Is RAB3GAP1 p.Arg231Ter (c.691C>T) pathogenic?

RAB3GAP1 p.Arg231Ter (c.691C>T) is classified Pathogenic in RAB3GAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-22). Very rare (popmax 0.00446%, eas).

How common is RAB3GAP1 p.Arg231Ter (c.691C>T) in the general population?

RAB3GAP1 p.Arg231Ter (c.691C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

RAB3GAP1 p.Arg231Ter

c.691C>T · rs1310680343 · VCV1338882

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.2	GERP 1.1, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,860 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00291% 47/1,613,080 alleles · very rare exomes 41/1,461,006 · genomes 6/152,074 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,430
European (non-Finnish)	0.00322%	31,033
Remaining individualsnot grpmax-eligible	0.0032%	31,227
Finnishnot grpmax-eligible	0.00312%	32,005
African / African-American	0.00267%	37,441
South Asian	0.0011%	91,046

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.Arg231Ter
Coding: c.691C>T
MANE Select: NM_012233
dbSNP: rs1310680343
Type: single nucleotide variant
Location: chr2:135120861 (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 231: a β-strand

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

Similar variants

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.Arg337Ter Pathogenic/Likely pathogenic ★★ same type
RAB3GAP1 p.Arg347Ter 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-arg231ter (accessed [today's date]).

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