Is RAB3GAP2 p.Ser761= (c.2283G>A) pathogenic?

RAB3GAP2 p.Ser761= (c.2283G>A) is classified Likely benign in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). Ultra-rare (popmax 0.0183%, amr); Associated with Warburg micro syndrome 2.

What condition is associated with RAB3GAP2 p.Ser761= (c.2283G>A)?

RAB3GAP2 p.Ser761= (c.2283G>A) is associated with Warburg micro syndrome 2, Martsolf syndrome (ClinVar).

How common is RAB3GAP2 p.Ser761= (c.2283G>A) in the general population?

RAB3GAP2 p.Ser761= (c.2283G>A) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

RAB3GAP2 p.Ser761=

c.2283G>A · rs757230922 · VCV2042124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

Warburg micro syndrome 2

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 -3.7	GERP -3.6
Overall
CADD	0.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/59,978 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00242% 39/1,613,818 alleles · ultra-rare exomes 32/1,461,798 · genomes 7/152,020 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,453
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,400
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,430
South Asian	0.0022%	45,538
European (non-Finnish)	0.00153%	65,553

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: RAB3GAP2
Protein: p.Ser761=
Coding: c.2283G>A
MANE Select: NM_012414
dbSNP: rs757230922
Type: single nucleotide variant
Location: chr1:220182284 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB

Full RAB3GAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Warburg micro syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Martsolf syndrome

Similar variants

RAB3GAP2 p.Ser761Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RAB3GAP2 c.713-2A>C Likely pathogenic ★★ same condition
RAB3GAP2 p.Arg1213Ter Pathogenic ★★ same condition
RAB3GAP2 p.Arg426Cys Pathogenic/Likely pathogenic ★★ same condition
RAB3GAP2 c.*2171A>G Uncertain significance ★★ same condition
RAB3GAP2 p.Ala16Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Ala240Pro Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Ala300Thr Uncertain significance ★★ ⚠ 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/rab3gap2-p-ser761 (accessed [today's date]).

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