Is RAB3GAP1 p.Phe12Ser (c.35T>C) pathogenic?

RAB3GAP1 p.Phe12Ser (c.35T>C) is classified Uncertain significance in RAB3GAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-28). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with Warburg micro syndrome 1.

What condition is associated with RAB3GAP1 p.Phe12Ser (c.35T>C)?

RAB3GAP1 p.Phe12Ser (c.35T>C) is associated with Warburg micro syndrome 1 (ClinVar).

How common is RAB3GAP1 p.Phe12Ser (c.35T>C) in the general population?

RAB3GAP1 p.Phe12Ser (c.35T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAB3GAP1 p.Phe12Ser (c.35T>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

RAB3GAP1 p.Phe12Ser

c.35T>C · rs1688906713 · VCV892874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Warburg micro syndrome 1

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 2% in RAB3GAP1
REVEL	0.546	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 82 kb · p 0.34 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAB3GAP1
Protein: p.Phe12Ser
Coding: c.35T>C
MANE Select: NM_012233
dbSNP: rs1688906713
Type: single nucleotide variant
Location: chr2:135052446 (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 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.Arg347Ter Pathogenic ★★ same condition
RAB3GAP1 p.Arg392Ter Pathogenic ★★ same condition
RAB3GAP1 p.Gln246Ter 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-phe12ser (accessed [today's date]).

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