Is RAB3GAP2 p.Asp427= (c.1281C>T) pathogenic?

RAB3GAP2 p.Asp427= (c.1281C>T) is classified Likely benign in RAB3GAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-25). Ultra-rare (popmax 0.0507%, mid); Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Asp427= (c.1281C>T)?

RAB3GAP2 p.Asp427= (c.1281C>T) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Asp427= (c.1281C>T) in the general population?

RAB3GAP2 p.Asp427= (c.1281C>T) is ultra-rare (popmax 0.0507%, mid) (gnomAD).

RAB3GAP2 p.Asp427=

c.1281C>T · rs372594666 · VCV518198

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, mid)

Conditions

Martsolf syndrome

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 -0.48	GERP -3
Overall
CADD	6.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0507% Middle Eastern · 3/5,912 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00473% 75/1,586,596 alleles · ultra-rare exomes 65/1,439,358 · genomes 10/147,238 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0507%	1,971
South Asian	0.011%	9,065
Admixed American	0.00858%	11,650
Remaining individualsnot grpmax-eligible	0.00493%	20,293
European (non-Finnish)	0.00438%	22,840
African / African-American	0.00276%	36,229
East Asian	0.00232%	43,100

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.Asp427=
Coding: c.1281C>T
MANE Select: NM_012414
dbSNP: rs372594666
Type: single nucleotide variant
Location: chr1:220191274 (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 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
RAB3GAP2 p.Ala684Glu 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-asp427 (accessed [today's date]).

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