Is RAB3GAP2 p.Pro993Arg (c.2978C>G) pathogenic?

RAB3GAP2 p.Pro993Arg (c.2978C>G) is classified Uncertain significance in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely benign (0.1067); Absent from gnomAD v4.1; Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Pro993Arg (c.2978C>G)?

RAB3GAP2 p.Pro993Arg (c.2978C>G) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Pro993Arg (c.2978C>G) in the general population?

RAB3GAP2 p.Pro993Arg (c.2978C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAB3GAP2 p.Pro993Arg (c.2978C>G)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Pro993Arg

c.2978C>G · rs2528634872 · VCV2163776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Martsolf syndrome

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -10.38	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 150 bp · p 0.00076 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAB3GAP2
Protein: p.Pro993Arg
Coding: c.2978C>G
MANE Select: NM_012414
dbSNP: rs2528634872
Type: single nucleotide variant
Location: chr1:220167504 (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

Martsolf syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Warburg micro syndrome 2

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-pro993arg (accessed [today's date]).

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