Is RAB3GAP2 p.Pro102Ser (c.304C>T) pathogenic?

RAB3GAP2 p.Pro102Ser (c.304C>T) is classified Uncertain significance in RAB3GAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-19). AlphaMissense: likely benign (0.1374); Ultra-rare (popmax 0.033%, mid); Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Pro102Ser (c.304C>T)?

RAB3GAP2 p.Pro102Ser (c.304C>T) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Pro102Ser (c.304C>T) in the general population?

RAB3GAP2 p.Pro102Ser (c.304C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts likely benign (score 0.1374) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Pro102Ser

c.304C>T · rs368861572 · VCV2062136

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1374 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Martsolf syndrome

Computational evidence

Protein change
AlphaMissense	0.1374	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 61 kb · p 0.2 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,056 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00167% 27/1,612,166 alleles · ultra-rare exomes 24/1,460,202 · genomes 3/151,964 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,028
East Asian	0.00446%	22,403
African / African-American	0.00401%	24,957
Admixed American	0.00334%	29,973
Remaining individualsnot grpmax-eligible	0.0032%	31,219
European (non-Finnish)	0.00127%	78,575
South Asian	0.0011%	91,022

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.Pro102Ser
Coding: c.304C>T
MANE Select: NM_012414
dbSNP: rs368861572
Type: single nucleotide variant
Location: chr1:220213856 (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-pro102ser (accessed [today's date]).

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