Is RAB3GAP1 p.Pro934Ser (c.2800C>T) pathogenic?

RAB3GAP1 p.Pro934Ser (c.2800C>T) is classified Conflicting classifications of pathogenicity in RAB3GAP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.3648); Rare (popmax 0.251%, afr).

How common is RAB3GAP1 p.Pro934Ser (c.2800C>T) in the general population?

RAB3GAP1 p.Pro934Ser (c.2800C>T) is rare (popmax 0.251%, afr) (gnomAD).

What do computational predictors say about RAB3GAP1 p.Pro934Ser (c.2800C>T)?

AlphaMissense predicts ambiguous (score 0.3648) — an in-silico prediction, not a clinical call.

RAB3GAP1 p.Pro934Ser

c.2800C>T · rs77535003 · VCV767426

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3648 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.251%, afr)

Computational evidence

Protein change
AlphaMissense	0.3648	ambiguous
REVEL	0.33	indeterminate
SaProt	LLR -7.32	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.47	GERP 0.42, phastCons 0.037
Regional constraint	o/e 1.02	unconstrained · MANE · 5,685 bp · p 0.84 · regional, not allelic
Overall
CADD	19.41	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 0.251% African / African-American · 188/75,038 alleles

Filtering AF 0.221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.21%

Overall 0.0173% 280/1,614,186 alleles · rare exomes 157/1,461,890 · genomes 123/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.251%	399
Admixed American	0.0683%	1,464
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.00439%	22,769
European (non-Finnish)	0.00212%	47,202

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.Pro934Ser
Coding: c.2800C>T
MANE Select: NM_012233
dbSNP: rs77535003
Type: single nucleotide variant
Location: chr2:135168635 (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 934: the 'disordered' region

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

Similar variants

RAB3GAP1 p.Pro934Ala Benign/Likely benign ★★ same residue
RAB3GAP1 p.Pro934Thr Uncertain significance ★ same residue
RAB3GAP1 p.Pro934His Likely benign ★ ⚠ same residue
RAB3GAP1 p.Pro934fs Pathogenic 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

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-pro934ser (accessed [today's date]).

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