Is RAB3GAP1 p.Arg347= (c.1041A>G) pathogenic?

RAB3GAP1 p.Arg347= (c.1041A>G) is classified Benign in RAB3GAP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Low-frequency (popmax 4.21%, afr); Associated with Warburg micro syndrome 1.

What condition is associated with RAB3GAP1 p.Arg347= (c.1041A>G)?

RAB3GAP1 p.Arg347= (c.1041A>G) is associated with Warburg micro syndrome 1 (ClinVar).

How common is RAB3GAP1 p.Arg347= (c.1041A>G) in the general population?

RAB3GAP1 p.Arg347= (c.1041A>G) is low-frequency (popmax 4.21%, afr) (gnomAD).

RAB3GAP1 p.Arg347=

c.1041A>G · rs77972211 · VCV130061

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.21%, afr)

Conditions

Warburg micro syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -2.9, phastCons 1
Overall
CADD	8.817	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.21% African / African-American · 3,151/74,924 alleles

Filtering AF 4.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.03%

Overall 0.22% 3,554/1,613,164 alleles · low-frequency exomes 1,762/1,461,026 · genomes 1,792/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.21%	24
Admixed American	0.298%	335
Remaining individualsnot grpmax-eligible	0.29%	345
Middle Eastern	0.0495%	2,019
South Asian	0.0209%	4,789
European (non-Finnish)	0.00178%	56,164

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: RAB3GAP1
Protein: p.Arg347=
Coding: c.1041A>G
MANE Select: NM_012233
dbSNP: rs77972211
Type: single nucleotide variant
Location: chr2:135130062 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.46 · 1 PDB

Full RAB3GAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Warburg micro syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB3GAP1 p.Arg347Ter Pathogenic ★★ same residue
RAB3GAP1 p.Arg347Gln Uncertain significance ★ ⚠ same residue
RAB3GAP1 c.2607-1G>C Pathogenic ★★ same condition
RAB3GAP1 c.748+1G>A Pathogenic ★★ same condition
RAB3GAP1 c.899+1G>A Pathogenic ★★ same condition
RAB3GAP1 p.Arg187Ter Pathogenic ★★ same condition
RAB3GAP1 p.Arg337Ter Pathogenic/Likely pathogenic ★★ same condition
RAB3GAP1 p.Arg392Ter Pathogenic ★★ 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/rab3gap1-p-arg347 (accessed [today's date]).

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