Is RAB3GAP2 p.Val201Met (c.601G>A) pathogenic?

RAB3GAP2 p.Val201Met (c.601G>A) is classified Uncertain significance in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.1527); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP2 p.Val201Met (c.601G>A)?

RAB3GAP2 p.Val201Met (c.601G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RAB3GAP2 p.Val201Met (c.601G>A) in the general population?

RAB3GAP2 p.Val201Met (c.601G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Val201Met (c.601G>A)?

AlphaMissense predicts likely benign (score 0.1527) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Val201Met

c.601G>A · rs971878780 · VCV3150754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1527	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -2.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 18 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00105% 17/1,613,742 alleles · very rare exomes 17/1,461,444 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,834
South Asiangrpmax	0.00329%	30,361
East Asian	0.00223%	44,876
European (non-Finnish)	0.000848%	117,963

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val201Met
Coding: c.601G>A
MANE Select: NM_012414
dbSNP: rs971878780
Type: single nucleotide variant
Location: chr1:220210399 (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

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

Similar variants

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RAB3GAP2 p.Asn1188Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn697Ser Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn960Asp Uncertain significance ★★ ⚠ same condition
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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-val201met (accessed [today's date]).

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