Is RAB3GAP2 p.Val1269Ala (c.3806T>C) pathogenic?

RAB3GAP2 p.Val1269Ala (c.3806T>C) is classified Uncertain significance in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely benign (0.0998); Ultra-rare (popmax 0.0423%, eas); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP2 p.Val1269Ala (c.3806T>C)?

RAB3GAP2 p.Val1269Ala (c.3806T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RAB3GAP2 p.Val1269Ala (c.3806T>C) in the general population?

RAB3GAP2 p.Val1269Ala (c.3806T>C) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Val1269Ala (c.3806T>C)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Val1269Ala

c.3806T>C · VCV3312165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.9, phastCons 0.004
Regional constraint	o/e 0.85	unconstrained · MANE · 16 kb · p 0.0014 · regional, not allelic
Overall
CADD	16.51	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 0.0423% East Asian · 19/44,890 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00124% 20/1,614,020 alleles · ultra-rare exomes 19/1,461,830 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,363
European (non-Finnish)	8.47e-05%	1,179,998

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.Val1269Ala
Coding: c.3806T>C
MANE Select: NM_012414
Type: single nucleotide variant
Location: chr1:220153246 (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

RAB3GAP2 p.Val1269Ile Uncertain significance ★★ ⚠ 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-val1269ala (accessed [today's date]).

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