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19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska Tag Q1_26_MOI tag was added to gene: AIPL1.
19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: Comment on list classification: There is limited evidence for the association of AIPL1 and autosomal dominant cone-rod dystrophy. The overwhelming majority of reported patients has biallelic AIPL1 variants, with heterozygous carriers being unaffected. Variant AIPL1 (p.Ala352_Pro355del) has the most supporting evidence for pathogenicity. However, the allele frequency in control populations is too high to cause dominant disease. In addition, the gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen. Based on available evidence, the MOI should be changed to BIALLELIC.; to: Comment on list classification: There is limited evidence for the association of AIPL1 and autosomal dominant cone-rod dystrophy. An overwhelming majority of reported patients harbour biallelic AIPL1 variants, with heterozygous carriers being unaffected. Variant p.Ala352_Pro355del in AIPL1 has the most supporting evidence for pathogenicity. However, the allele frequency in control populations is too high to cause dominant disease (MAF = 0.01129). In addition, the gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen. Based on available evidence, the MOI should be changed to BIALLELIC.
19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. Method: WES in proband, Sanger seq in family members. The same mutation (p.W278X) was found in homozygosity in 5 Italian families and in compound het state with another AIPL1 mutation in 3 other families with recessive LCA (PMID: 21474771). Unlikely to be pathogenic dominant. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease. Supporting functional evidence: PMID: 33067476 Sacristan-Reviriego et al., 2020 - poses that this deletion has an alternative pathogenicity mechanism: PRD-mediated dominant negative effect causing cone-rod dystrophy PMID: 25274777 Ku et al., 2015 - mouse model where p.A352_P355del human AIPL1 transgene was expressed in an Aipl1 null background. In single transgenic mice, the mutant transgene led to a cone-rod dystrophy phenotype, predominantly leading to a slow and progressive cone degeneration. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 21900377 Pennesi et al., 2011 Family 1: patient was found to have a homozygous Trp278 stop mutation in AIPL1; family 2: two siblings were compound heterozygous for AIPL1 (Leu17Pro and Lys214Asn). Variants confirmed in trans, het parents and sister unaffected. Sequenced 14 LCA-causing genes. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. Method: WES in proband, Sanger seq in family members. The same mutation (p.W278X) was found in homozygosity in 5 Italian families and in compound het state with another AIPL1 mutation in 3 other families with recessive LCA (PMID: 21474771). Unlikely to be pathogenic dominant. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease. Supporting functional evidence: PMID: 33067476 Sacristan-Reviriego et al., 2020 - poses that this deletion has an alternative pathogenicity mechanism: PRD-mediated dominant negative effect causing cone-rod dystrophy PMID: 25274777 Ku et al., 2015 - mouse model where p.A352_P355del human AIPL1 transgene was expressed in an Aipl1 null background. In single transgenic mice, the mutant transgene led to a cone-rod dystrophy phenotype, predominantly leading to a slow and progressive cone degeneration. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. PMID: 21900377 Pennesi et al., 2011 Family 1: patient was found to have a homozygous Trp278 stop mutation in AIPL1; family 2: two siblings were compound heterozygous for AIPL1 (Leu17Pro and Lys214Asn). Variants confirmed in trans, het parents and sister unaffected. Sequenced 14 LCA-causing genes. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.
19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska edited their review of gene: AIPL1: Added comment: Comment on list classification: There is limited evidence for the association of AIPL1 and autosomal dominant cone-rod dystrophy. The overwhelming majority of reported patients has biallelic AIPL1 variants, with heterozygous carriers being unaffected. Variant AIPL1 (p.Ala352_Pro355del) has the most supporting evidence for pathogenicity. However, the allele frequency in control populations is too high to cause dominant disease. In addition, the gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen. Based on available evidence, the MOI should be changed to BIALLELIC.; Changed publications to: 10873396, 15249368, 21474771, 21900377, 24426771, 25274777, 31576779, 33067476, 38880373; Changed phenotypes to: Leber congenital amaurosis 4, OMIM:604393, Leber congenital amaurosis, MONDO:0018998
19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 21900377 Pennesi et al., 2011 The first patient was found to have a homozygous Trp278 stop mutation in AIPL1, whereas the siblings were each found to have novel heterozygous mutations in AIPL1 (Leu17Pro and Lys214Asn). Sequenced 14 LCA-causing genes. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. Method: WES in proband, Sanger seq in family members. The same mutation (p.W278X) was found in homozygosity in 5 Italian families and in compound het state with another AIPL1 mutation in 3 other families with recessive LCA (PMID: 21474771). Unlikely to be pathogenic dominant. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease. Supporting functional evidence: PMID: 33067476 Sacristan-Reviriego et al., 2020 - poses that this deletion has an alternative pathogenicity mechanism: PRD-mediated dominant negative effect causing cone-rod dystrophy PMID: 25274777 Ku et al., 2015 - mouse model where p.A352_P355del human AIPL1 transgene was expressed in an Aipl1 null background. In single transgenic mice, the mutant transgene led to a cone-rod dystrophy phenotype, predominantly leading to a slow and progressive cone degeneration. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 21900377 Pennesi et al., 2011 Family 1: patient was found to have a homozygous Trp278 stop mutation in AIPL1; family 2: two siblings were compound heterozygous for AIPL1 (Leu17Pro and Lys214Asn). Variants confirmed in trans, het parents and sister unaffected. Sequenced 14 LCA-causing genes. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.
19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 21900377 Pennesi et al., 2011 The first patient was found to have a homozygous Trp278 stop mutation in AIPL1, whereas the siblings were each found to have novel heterozygous mutations in AIPL1 (Leu17Pro and Lys214Asn). Sequenced 14 LCA-causing genes. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.
19 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141 (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).
13 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).; to: PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).
13 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: PMID: 33067476 Sacristan-Reviriego A, et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).; to: PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).
13 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska changed review comment from: PMID: 33067476 Sacristan-Reviriego A, et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported; to: PMID: 33067476 Sacristan-Reviriego A, et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).
13 Jan 2026	Retinal disorders v8.78	AIPL1	Ida Ertmanska reviewed gene: AIPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33067476; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
10 Oct 2023	Retinal disorders v4.34	AIPL1	Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: AIPL1.
10 Oct 2023	Retinal disorders v4.34	AIPL1	Achchuthan Shanmugasundram reviewed gene: AIPL1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
10 Oct 2023	Retinal disorders v4.33	AIPL1	Achchuthan Shanmugasundram Mode of inheritance for gene AIPL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
22 Nov 2022	Retinal disorders v2.301	AIPL1	Arina Puzriakova Tag Q4_22_MOI tag was added to gene: AIPL1.
22 Nov 2022	Retinal disorders v2.301	AIPL1	Arina Puzriakova edited their review of gene: AIPL1: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
22 Nov 2022	Retinal disorders v2.301	AIPL1	Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): Achromatopsia, Cone, and Cone-rod Dystrophy; Cone-rod dystrophy (AD); Leber congenital amaurosis 4 (AR); Retinitis pigmentosa, juvenile (AD); Leber Congenital Amaurosis; Leber congenital amaurosis; Leber congenital amaurosis 4, 604393; Retinitis pigmentosa, juvenile, 604393; Cone-rod dystrophy, 604393; Eye Disorders; Retinitis Pigmentosa, Dominant; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa
22 Nov 2022	Retinal disorders v2.301	AIPL1	Arina Puzriakova Phenotypes for gene: AIPL1 were changed from Achromatopsia, Cone, and Cone-rod Dystrophy; Cone-rod dystrophy (AD); Leber congenital amaurosis 4 (AR); Retinitis pigmentosa, juvenile (AD); Leber Congenital Amaurosis; Leber congenital amaurosis; Leber congenital amaurosis 4, 604393; Retinitis pigmentosa, juvenile, 604393; Cone-rod dystrophy, 604393; Eye Disorders; Retinitis Pigmentosa, Dominant; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa to Cone-rod dystrophy, OMIM:604393; Retinitis pigmentosa, juvenile, OMIM:604393; Leber congenital amaurosis 4, OMIM:604393
22 Nov 2022	Retinal disorders v2.300	AIPL1	Arina Puzriakova Publications for gene: AIPL1 were set to
22 Nov 2022	Retinal disorders v2.299	AIPL1	Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'biallelic' to 'both mono- and biallelic (but biallelic mutations cause a more SEVERE disease form) at the next GMS panel update. This gene is typically associated with recessive inheritance of a Leber congenital amaurosis (LCA) phenotype. However, some patients with heterozygous variants have also been identified, usually presenting less severe phenotypes within the retinal dystrophy spectrum such as retinitis pigmentosa and rod-cone dystrophy/dysfunction - although heterozygous variants act with reduced penetrance (PMID: 10873396; 15249368; 21900377; 33067476) Both MOIs are also listed in OMIM.
22 Nov 2022	Retinal disorders v2.299	AIPL1	Arina Puzriakova Mode of inheritance for gene: AIPL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
30 Aug 2019	Retinal disorders v1.159	AIPL1	Gavin Arno reviewed gene: AIPL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
03 Apr 2019	Retinal disorders v1.137	AIPL1	Ivone Leong Source NHS GMS was added to AIPL1. Rating Changed from Green List (high evidence) to Green List (high evidence)
17 Jan 2017	Retinal disorders	AIPL1	BRIDGE consortium reviewed AIPL1