Early onset or syndromic epilepsy

Gene: SF3B1

Green List (high evidence)

Comment on list classification: There are now numerous individuals reported with monoallelic (mostly de novo) variants in SF3B1 presenting with syndromic ID/GDD, with 13 individuals reported to have seizures. Based on available evidence, this gene can be promoted to Green at the next update.

Created: 25 Jun 2026, 3:01 p.m. | Last Modified: 25 Jun 2026, 4:39 p.m.

Panel Version: 9.17

As reviewed by Karen Stals, Uguen et al. (PMID: 41577671, 2026) reported 26 patients with heterozygous SF3B1 variants. Most of them were confirmed to be de novo, with 3 cases where variant was inherited from a parent (2 parents with learning difficulties, and 1 asymptomatic father). Seq method: Trio or Solo WES. 3 patients had VUS variants in other genes.
"Almost all (23/26) affected individuals exhibited at least one neurodevelopmental abnormality, the most frequent being language delay (21/26). Motor delay was found in 18/24 individuals. Intellectual disability (ID) was present in 9/15 individuals, some cases being too young (8/26) to assess. The severity of ID was mainly mild to moderate, only two individuals presenting with severe ID. Seizures were reported in 13 individuals, with variable ages of onset and types." Other features: hypotonia (11 patients), spastic quadriplegia (2 patients without NDD), non-specific brain MRI anomalies (4 cases), cleft palate or high-arched palate (12 patients), heart defects (8/25), postnatal short stature (6), IUGR (5), microcephaly (7/22 assessed).

De novo missense variants in the SF3B1 gene have also been identified in ASD probands (PMID: 25363768 Iossifov et al., 2014 - 2 probands with ASD, harbouring SF3B1 variants c.1078A>G, p.Ile360Val & c.890C>A, p.Pro297His) and two probands with unspecified developmental disorders, with de novo SF3B1 variants c.1108C>T, p.Pro370Ser & c.1781G>A, p.Arg594Gln (PMID: 28135719 Deciphering Developmental Disorders Study 2017).

SF3B1 is not yet associated with an NDD in OMIM, and it has not been classified in ClinGen (accessed 17th Jun 2026). The gene is Green in PanelApp Australia on 'Intellectual disability syndromic and non-syndromic' panel.
Sources: Literature

Created: 25 Jun 2026, 2:58 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Complex neurodevelopmental disorder, MONDO:0100038

Publications

• 25363760
• 28135719
• 41577671