Is RAB3GAP2 p.Ile726Val (c.2176A>G) pathogenic?

RAB3GAP2 p.Ile726Val (c.2176A>G) is classified Conflicting classifications of pathogenicity in RAB3GAP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-10-25). AlphaMissense: likely benign (0.0623); Ultra-rare (popmax 0.0494%, afr); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP2 p.Ile726Val (c.2176A>G)?

RAB3GAP2 p.Ile726Val (c.2176A>G) is associated with Inborn genetic diseases, Warburg micro syndrome 2, Martsolf syndrome (ClinVar).

How common is RAB3GAP2 p.Ile726Val (c.2176A>G) in the general population?

RAB3GAP2 p.Ile726Val (c.2176A>G) is ultra-rare (popmax 0.0494%, afr) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Ile726Val (c.2176A>G)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Ile726Val

c.2176A>G · rs148513462 · VCV1188577

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.38	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 -3.2	GERP -3.6
Regional constraint	o/e 0.99	unconstrained · MANE · 26 kb · p 0.76 · regional, not allelic
Overall
CADD	0.05	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 0.0494% African / African-American · 37/74,922 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00801% 129/1,610,374 alleles · ultra-rare exomes 101/1,458,044 · genomes 28/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0494%	2,025
Middle Eastern	0.0199%	5,024
Remaining individualsnot grpmax-eligible	0.00803%	12,461
European (non-Finnish)	0.00704%	14,207
Admixed American	0.00501%	19,941

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.Ile726Val
Coding: c.2176A>G
MANE Select: NM_012414
dbSNP: rs148513462
Type: single nucleotide variant
Location: chr1:220182754 (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

Also linked: Warburg micro syndrome 2 Martsolf syndrome

Similar variants

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
RAB3GAP2 p.Ala684Glu 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-ile726val (accessed [today's date]).

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