Is RAB3GAP1 p.Phe686fs (c.2037_2055dup) pathogenic?

RAB3GAP1 p.Phe686fs (c.20372055dup) is classified Pathogenic in RAB3GAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-05-01). Very rare (popmax 0.00102%, nfe); Associated with Warburg micro syndrome 1.

What condition is associated with RAB3GAP1 p.Phe686fs (c.2037_2055dup)?

RAB3GAP1 p.Phe686fs (c.2037_2055dup) is associated with Warburg micro syndrome 1 (ClinVar).

How common is RAB3GAP1 p.Phe686fs (c.2037_2055dup) in the general population?

RAB3GAP1 p.Phe686fs (c.2037_2055dup) is very rare (popmax 0.00102%, nfe) (gnomAD).

RAB3GAP1 p.Phe686fs

c.2037_2055dup · rs587777153 · VCV100770

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

Warburg micro syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 18 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,014 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,868 alleles · very rare

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.Phe686fs
Coding: c.2037_2055dup
MANE Select: NM_012233
dbSNP: rs587777153
Type: Duplication
Location: chr2:135150477 (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 p.Lys144Ter Pathogenic/Likely pathogenic ★★ same condition
RAB3GAP1 p.Cys181fs Likely pathogenic ★ same condition
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

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-phe686fs (accessed [today's date]).

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