Is RAB3GAP2 p.Val477Met (c.1429G>A) pathogenic?

RAB3GAP2 p.Val477Met (c.1429G>A) is classified Uncertain significance in RAB3GAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.6061); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP2 p.Val477Met (c.1429G>A)?

RAB3GAP2 p.Val477Met (c.1429G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RAB3GAP2 p.Val477Met (c.1429G>A) in the general population?

RAB3GAP2 p.Val477Met (c.1429G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Val477Met (c.1429G>A)?

AlphaMissense predicts likely pathogenic (score 0.6061) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Val477Met

c.1429G>A · VCV4056066

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6061	likely pathogenic
REVEL	0.701	pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 26 kb · p 0.76 · regional, not allelic
Overall
CADD	27.6	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 · 1/6,052 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000743% 12/1,614,086 alleles · ultra-rare exomes 8/1,461,816 · genomes 4/152,270 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
African / African-American	0.00933%	10,719
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	8.47e-05%	1,179,980

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.Val477Met
Coding: c.1429G>A
MANE Select: NM_012414
Type: single nucleotide variant
Location: chr1:220191126 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB
Residue 477: a β-strand

Full RAB3GAP2 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

Similar variants

RAB3GAP2 p.Val477= Likely benign ★ same residue
RAB3GAP2 p.Arg1032Cys Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Arg35Trp Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Arg415Lys Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn1188Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn697Ser Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn960Asp Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asp1114Asn 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-val477met (accessed [today's date]).

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