Is SYNGAP1 p.Pro1104= (c.3312A>C) pathogenic?

SYNGAP1 p.Pro1104= (c.3312A>C) is classified Likely benign in SYNGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-18). Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 5.

What condition is associated with SYNGAP1 p.Pro1104= (c.3312A>C)?

SYNGAP1 p.Pro1104= (c.3312A>C) is associated with intellectual disability, autosomal dominant 5 (ClinVar).

How common is SYNGAP1 p.Pro1104= (c.3312A>C) in the general population?

SYNGAP1 p.Pro1104= (c.3312A>C) is absent from gnomAD v4.1 (gnomAD).

SYNGAP1 p.Pro1104=

Q: How is SYNGAP1-related developmental and epileptic encephalopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.3312A>C · rs2537452947 · VCV2718908

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, autosomal dominant 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.21	GERP -2.7, phastCons 0.006
Overall
CADD	1.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SYNGAP1
Protein: p.Pro1104=
Coding: c.3312A>C
MANE Select: NM_006772
dbSNP: rs2537452947
Type: single nucleotide variant
Location: chr6:33443864 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.43
Residue 1104: a UniProt-annotated variant site (in mrd5; uncertain significance); a UniProt-annotated variant site (in mrd5); the 'disordered' region

Full SYNGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For SYNGAP1-related developmental and epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

SYNGAP1 p.Pro1104Ser Benign ★ same residue
SYNGAP1 c.1532-1G>A Pathogenic/Likely pathogenic ★★ same condition
SYNGAP1 c.1676+1G>A Pathogenic/Likely pathogenic ★★ same condition
SYNGAP1 c.2294+1G>T Pathogenic ★★ same condition
SYNGAP1 c.3583-1G>A Likely pathogenic ★★ same condition
SYNGAP1 c.3583-6G>A Pathogenic/Likely pathogenic ★★ same condition
SYNGAP1 c.3583-9G>A Pathogenic ★★ same condition
SYNGAP1 c.509+1G>T Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/syngap1-p-pro1104 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown