SYNGAP1 (Q96PV0) variants and mutations

SYNGAP1 (also known as Q96PV0) is a human protein-coding gene encoding a ras/Rap GTPase-activating protein SynGAP protein. It restrains RAS-family signaling at excitatory synapses and is critical for activity-dependent synaptic maturation and plasticity. Haploinsufficiency causes SYNGAP1-related neurodevelopmental disorder, typically with intellectual disability, generalized epilepsy, behavioral abnormalities, and severe speech impairment. This analysis covers 1,807 SYNGAP1 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes intellectual disability, autosomal dominant 5, complex neurodevelopmental disorder, and hereditary disease. Example SYNGAP1 variants include M1I, S2N, and p.Ser2del.

Variant analysis overview

Gene: SYNGAP1
Protein: Q96PV0
UniProt accession: Q96PV0
Organism: Homo sapiens
Variants analyzed: 1807
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 1,660 unspecified-consequence records; 1 in-frame deletions; 87 missense variants; 52 synonymous variants; 2 frameshift variants; 2 splice-region variants; 1 stop-gained variants; 2 substitution
Prediction scores: 1,193 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, autosomal dominant 5, complex neurodevelopmental disorder, hereditary disease, Intellectual disability, Seizure, Epileptic encephalopathy, neurodevelopmental disorder, epilepsy with myoclonic atonic seizures, Global developmental delay, developmental disability, Delayed speech and language development, Neurodevelopmental delay.

Protein structure and variant hotspots

Protein features: 3 domains; 27 post-translational modification sites.
Structural context: 524 variants have structural context.
PTM context: 39 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SYNGAP1 variants

Examples include M1I, S2N, p.Ser2del, S2G, S2I, S2T, S2S, S2R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SYNGAP1 analysis run — SYNGAP1 (1,807 variants) — completed 2026-08-19