Is RAB3GAP2 p.Val1234= (c.3702C>T) pathogenic?

RAB3GAP2 p.Val1234= (c.3702C>T) is classified Conflicting classifications of pathogenicity in RAB3GAP2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-26). Rare (popmax 0.127%, afr); Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Val1234= (c.3702C>T)?

RAB3GAP2 p.Val1234= (c.3702C>T) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Val1234= (c.3702C>T) in the general population?

RAB3GAP2 p.Val1234= (c.3702C>T) is rare (popmax 0.127%, afr) (gnomAD).

RAB3GAP2 p.Val1234=

c.3702C>T · rs137897304 · VCV286109

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.127%, afr)

Conditions

Martsolf syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.88, phastCons 1
Overall
CADD	6.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.127% African / African-American · 95/75,050 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0982%

Overall 0.00657% 106/1,614,164 alleles · rare exomes 47/1,461,870 · genomes 59/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.127%	790
Admixed American	0.0117%	8,574
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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.Val1234=
Coding: c.3702C>T
MANE Select: NM_012414
dbSNP: rs137897304
Type: single nucleotide variant
Location: chr1:220153350 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB

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

Disease context

Martsolf syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Warburg micro syndrome 2

Similar variants

RAB3GAP2 p.Val1234Ala Uncertain significance ★★ ⚠ same residue
RAB3GAP2 c.713-2A>C Likely pathogenic ★★ same condition
RAB3GAP2 p.Arg1213Ter Pathogenic ★★ same condition
RAB3GAP2 p.Arg426Cys Pathogenic/Likely pathogenic ★★ same condition
RAB3GAP2 c.*2171A>G Uncertain significance ★★ same condition
RAB3GAP2 p.Ala16Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Ala240Pro Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Ala300Thr Uncertain significance ★★ ⚠ 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/rab3gap2-p-val1234 (accessed [today's date]).

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