SMARCA2 (P51531) variants and mutations

SMARCA2 (also known as P51531) is a human protein-coding gene encoding a SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 protein. It provides ATP-dependent nucleosome remodeling activity to selected SWI/SNF complexes and helps control transcriptional access to chromatin. Heterozygous pathogenic variants cause Nicolaides-Baraitser syndrome or, through distinct mechanisms, blepharophimosis-intellectual-disability syndrome. This analysis covers 2,169 SMARCA2 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes intellectual disability-sparse hair-brachydactyly syndrome, intellectual disability - sparse hair - brachydactyly, and blepharophimosis-impaired intellectual development syndrome. Example SMARCA2 variants include S2F, S2A, and S2Y.

Variant analysis overview

Gene: SMARCA2
Protein: P51531
UniProt accession: P51531
Organism: Homo sapiens
Variants analyzed: 2169
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 1,850 unspecified-consequence records; 151 missense variants; 114 synonymous variants; 14 frameshift variants; 5 stop-gained variants; 1 protein altering variant; 17 in-frame deletions; 1 splice-region variants; 12 in-frame insertions; 4 substitution
Prediction scores: 1,437 variants have prediction scores (66% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: intellectual disability-sparse hair-brachydactyly syndrome, intellectual disability - sparse hair - brachydactyly, blepharophimosis-impaired intellectual development syndrome, hereditary disease, Intellectual disability, blepharophimosis - intellectual disability syndrome, Coffin-Siris syndrome, Blepharophimosis-intellectual disability syndrome, neurodevelopmental disorder, gestational diabetes, Neurodevelopmental delay, vein of Galen aneurysm.

Protein structure and variant hotspots

Protein features: 5 domains; 3 binding sites; 18 post-translational modification sites.
Structural context: 642 variants have structural context.
PTM context: 25 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SMARCA2 variants

Examples include S2F, S2A, S2Y, S2C, T3M, T3K, T3T, P4L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SMARCA2 analysis run — SMARCA2 (2,169 variants) — completed 2026-08-20