Is SYNGAP1 p.Pro787= (c.2361C>T) pathogenic?

SYNGAP1 p.Pro787= (c.2361C>T) is classified Likely benign in SYNGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Very rare (popmax 0.00297%, nfe); Associated with intellectual disability, autosomal dominant 5.

What condition is associated with SYNGAP1 p.Pro787= (c.2361C>T)?

SYNGAP1 p.Pro787= (c.2361C>T) is associated with intellectual disability, autosomal dominant 5 (ClinVar).

How common is SYNGAP1 p.Pro787= (c.2361C>T) in the general population?

SYNGAP1 p.Pro787= (c.2361C>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

SYNGAP1 p.Pro787=

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.2361C>T · rs775679543 · VCV1204702

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -2.6, phastCons 0.51
Overall
CADD	5.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,179,876 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00235% 38/1,613,726 alleles · very rare exomes 35/1,461,742 · genomes 3/151,984 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,711
South Asian	0.0022%	45,532
Remaining individualsnot grpmax-eligible	0.0016%	62,474

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SYNGAP1
Protein: p.Pro787=
Coding: c.2361C>T
MANE Select: NM_006772
dbSNP: rs775679543
Type: single nucleotide variant
Location: chr6:33442913 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.43
Residue 787: 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.Pro787Ser Uncertain significance ★ ⚠ same residue
SYNGAP1 p.Pro787Thr Likely benign ★ ⚠ same residue
SYNGAP1 p.Pro787fs Pathogenic ★ 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

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-pro787 (accessed [today's date]).

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