Is RAB3GAP1 p.Arg892Ser (c.2676G>T) pathogenic?

RAB3GAP1 p.Arg892Ser (c.2676G>T) is classified Conflicting classifications of pathogenicity in RAB3GAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1571); Low-frequency (popmax 1.12%, afr).

How common is RAB3GAP1 p.Arg892Ser (c.2676G>T) in the general population?

RAB3GAP1 p.Arg892Ser (c.2676G>T) is low-frequency (popmax 1.12%, afr) (gnomAD).

What do computational predictors say about RAB3GAP1 p.Arg892Ser (c.2676G>T)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

RAB3GAP1 p.Arg892Ser

c.2676G>T · rs144455066 · VCV211980

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -9.12	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 0.18	GERP -2.1, phastCons 0.8
Regional constraint	o/e 1.02	unconstrained · MANE · 5,685 bp · p 0.84 · regional, not allelic
Overall
CADD	11.83	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 1.12% African / African-American · 838/74,984 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0563% 908/1,612,968 alleles · low-frequency exomes 488/1,460,734 · genomes 420/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.12%	89
Remaining individualsnot grpmax-eligible	0.0608%	1,644
Admixed American	0.0417%	2,400
South Asian	0.0033%	30,337
European (non-Finnish)	0.000339%	294,809

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.Arg892Ser
Coding: c.2676G>T
MANE Select: NM_012233
dbSNP: rs144455066
Type: single nucleotide variant
Location: chr2:135164663 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.46 · 1 PDB
Residue 892: an α-helix

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

Similar variants

RAB3GAP1 p.Arg892Gly Uncertain significance ★★ ⚠ same residue
RAB3GAP1 c.18+1G>C Likely pathogenic ★★ same type
RAB3GAP1 c.2607-1G>C Pathogenic ★★ same type
RAB3GAP1 c.748+1G>A Pathogenic ★★ same type
RAB3GAP1 c.899+1G>A Pathogenic ★★ same type
RAB3GAP1 p.Arg174Ter Pathogenic/Likely pathogenic ★★ same type
RAB3GAP1 p.Arg187Ter Pathogenic ★★ same type
RAB3GAP1 p.Arg231Ter Pathogenic ★★ same type

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-arg892ser (accessed [today's date]).

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