Is RAB3GAP2 p.Arg232Gln (c.695G>A) pathogenic?

RAB3GAP2 p.Arg232Gln (c.695G>A) is classified Uncertain significance in RAB3GAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-07). AlphaMissense: likely pathogenic (0.8561); Ultra-rare (popmax 0.0165%, mid); Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Arg232Gln (c.695G>A)?

RAB3GAP2 p.Arg232Gln (c.695G>A) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Arg232Gln (c.695G>A) in the general population?

RAB3GAP2 p.Arg232Gln (c.695G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Arg232Gln (c.695G>A)?

AlphaMissense predicts likely pathogenic (score 0.8561) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Arg232Gln

c.695G>A · rs189134236 · VCV875250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8561 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Martsolf syndrome

Computational evidence

Protein change
AlphaMissense	0.8561	likely pathogenic
REVEL	0.356	indeterminate
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 18 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00293% 47/1,605,760 alleles · ultra-rare exomes 45/1,453,718 · genomes 2/152,042 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,855
East Asian	0.00895%	11,171
Admixed American	0.00834%	11,992
African / African-American	0.00401%	24,923
European (non-Finnish)	0.00256%	39,096
Remaining individualsnot grpmax-eligible	0.00161%	62,220

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.Arg232Gln
Coding: c.695G>A
MANE Select: NM_012414
dbSNP: rs189134236
Type: single nucleotide variant
Location: chr1:220205924 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB
Residue 232: an α-helix

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

Disease context

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

Also linked: Warburg micro syndrome 2

Similar variants

RAB3GAP2 p.Arg232Ter Pathogenic ★ 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-arg232gln (accessed [today's date]).

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