Is RAB3GAP2 p.Ile29Ser (c.86T>G) pathogenic?

RAB3GAP2 p.Ile29Ser (c.86T>G) is classified Uncertain significance in RAB3GAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.057); Ultra-rare (popmax 0.0872%, eas); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP2 p.Ile29Ser (c.86T>G)?

RAB3GAP2 p.Ile29Ser (c.86T>G) is associated with Inborn genetic diseases, Warburg micro syndrome 2, Martsolf syndrome (ClinVar).

How common is RAB3GAP2 p.Ile29Ser (c.86T>G) in the general population?

RAB3GAP2 p.Ile29Ser (c.86T>G) is ultra-rare (popmax 0.0872%, eas) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Ile29Ser (c.86T>G)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Ile29Ser

c.86T>G · rs189536938 · VCV874387

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0872%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -3.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -2.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 61 kb · p 0.2 · regional, not allelic
Overall
CADD	16.77	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 0.0872% East Asian · 39/44,706 alleles

Filtering AF 0.0655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00248% 40/1,610,176 alleles · ultra-rare exomes 37/1,458,704 · genomes 3/151,472 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0872%	1,146
European (non-Finnish)	8.48e-05%	1,178,978

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.Ile29Ser
Coding: c.86T>G
MANE Select: NM_012414
dbSNP: rs189536938
Type: single nucleotide variant
Location: chr1:220272252 (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-ile29ser (accessed [today's date]).

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