Is RAB3GAP2 p.Pro1333= (c.3999C>T) pathogenic?

RAB3GAP2 p.Pro1333= (c.3999C>T) is classified Benign/Likely benign in RAB3GAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-08). Rare (popmax 0.164%, sas); Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Pro1333= (c.3999C>T)?

RAB3GAP2 p.Pro1333= (c.3999C>T) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Pro1333= (c.3999C>T) in the general population?

RAB3GAP2 p.Pro1333= (c.3999C>T) is rare (popmax 0.164%, sas) (gnomAD).

RAB3GAP2 p.Pro1333=

c.3999C>T · rs539609673 · VCV518168

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.164%, sas)

Conditions

Martsolf syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.33	GERP -1.1, phastCons 0.013
Overall
CADD	5.975	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% South Asian · 149/91,014 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0105% 170/1,611,996 alleles · rare exomes 163/1,459,742 · genomes 7/152,254 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.164%	611
Remaining individualsnot grpmax-eligible	0.0272%	3,673
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000255%	392,693

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.Pro1333=
Coding: c.3999C>T
MANE Select: NM_012414
dbSNP: rs539609673
Type: single nucleotide variant
Location: chr1:220151633 (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-pro1333 (accessed [today's date]).

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