Is SYNGAP1 p.Pro1065= (c.3195G>A) pathogenic?

SYNGAP1 p.Pro1065= (c.3195G>A) is classified Likely benign in SYNGAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with SYNGAP1 p.Pro1065= (c.3195G>A)?

SYNGAP1 p.Pro1065= (c.3195G>A) is associated with Inborn genetic diseases, intellectual disability, autosomal dominant 5 (ClinVar).

How common is SYNGAP1 p.Pro1065= (c.3195G>A) in the general population?

SYNGAP1 p.Pro1065= (c.3195G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

SYNGAP1 p.Pro1065=

c.3195G>A · rs752562193 · VCV469155

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

Inborn genetic diseases

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 -4.7	GERP -2.4
Overall
CADD	1.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,832 alleles

Filtering AF 0.00452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00413%

Overall 0.00485% 78/1,608,040 alleles · ultra-rare exomes 76/1,456,026 · genomes 2/152,014 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,972
European (non-Finnish)	0.00561%	17,828
South Asian	0.0033%	30,299
Remaining individualsnot grpmax-eligible	0.00321%	31,126
East Asian	0.00223%	44,766

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.Pro1065=
Coding: c.3195G>A
MANE Select: NM_006772
dbSNP: rs752562193
Type: single nucleotide variant
Location: chr6:33443747 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.43
Residue 1065: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, autosomal dominant 5

Similar variants

SYNGAP1 p.Pro1065Leu Likely benign ★ same residue
SYNGAP1 p.Pro1065fs 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
SYNGAP1 c.3583-9G>A 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-pro1065 (accessed [today's date]).

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