Is RAB3GAP2 p.Ile467= (c.1401C>A) pathogenic?

RAB3GAP2 p.Ile467= (c.1401C>A) is classified Likely benign in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). Very rare (popmax 0.00144%, nfe).

How common is RAB3GAP2 p.Ile467= (c.1401C>A) in the general population?

RAB3GAP2 p.Ile467= (c.1401C>A) is very rare (popmax 0.00144%, nfe) (gnomAD).

RAB3GAP2 p.Ile467=

c.1401C>A · VCV4940916

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

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 3.9	GERP -0.12, phastCons 1
Overall
CADD	8.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,179,970 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00979% 158/1,613,922 alleles · very rare exomes 123/1,461,832 · genomes 35/152,090 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.214%	467
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)grpmax	0.00144%	69,410

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile467=
Coding: c.1401C>A
MANE Select: NM_012414
Type: single nucleotide variant
Location: chr1:220191154 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB
Residue 467: a β-strand

Full RAB3GAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB3GAP2 c.713-2A>C Likely pathogenic ★★ same type
RAB3GAP2 p.Arg1213Ter Pathogenic ★★ same type
RAB3GAP2 p.Arg426Cys Pathogenic/Likely pathogenic ★★ same type
RAB3GAP2 c.1631+8G>T Uncertain significance ★★ same type
RAB3GAP2 c.*2171A>G Uncertain significance ★★ same type
RAB3GAP2 p.Ala16Thr Uncertain significance ★★ ⚠ same type
RAB3GAP2 p.Ala240Pro Uncertain significance ★★ ⚠ same type
RAB3GAP2 p.Ala300Thr Uncertain significance ★★ ⚠ 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/rab3gap2-p-ile467 (accessed [today's date]).

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