Is RAB3GAP2 p.Ser4Pro (c.10T>C) pathogenic?

RAB3GAP2 p.Ser4Pro (c.10T>C) is classified Uncertain significance in RAB3GAP2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6769); Ultra-rare (popmax 0.0357%, eas); Associated with microcephaly.

What condition is associated with RAB3GAP2 p.Ser4Pro (c.10T>C)?

RAB3GAP2 p.Ser4Pro (c.10T>C) is associated with microcephaly (ClinVar).

How common is RAB3GAP2 p.Ser4Pro (c.10T>C) in the general population?

RAB3GAP2 p.Ser4Pro (c.10T>C) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Ser4Pro (c.10T>C)?

AlphaMissense predicts likely pathogenic (score 0.6769) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Ser4Pro

c.10T>C · rs773666005 · VCV813550

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6769 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly

Computational evidence

Protein change
AlphaMissense	0.6769	likely pathogenic
REVEL	0.197	benign-leaning
SaProt	LLR -12.58	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 61 kb · p 0.2 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.0357% East Asian · 16/44,772 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.000993% 16/1,610,474 alleles · ultra-rare exomes 15/1,458,760 · genomes 1/151,714 · joint denominator

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.Ser4Pro
Coding: c.10T>C
MANE Select: NM_012414
dbSNP: rs773666005
Type: single nucleotide variant
Location: chr1:220272328 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB
Residue 4: a β-strand

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

Disease context

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

Similar variants

RAB3GAP2 p.Arg385Cys Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Leu174Val Uncertain significance ★ ⚠ same condition
RAB3GAP2 c.713-2A>C Likely pathogenic ★★ same type
RAB3GAP2 p.Arg1213Ter Pathogenic ★★ same type
RAB3GAP2 p.Arg426Cys Pathogenic/Likely pathogenic ★★ same type
RAB3GAP2 c.1631+8G>T Uncertain significance ★★ same type
RAB3GAP2 c.*2171A>G Uncertain significance ★★ same type
RAB3GAP2 p.Ala16Thr Uncertain significance ★★ ⚠ same type

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-ser4pro (accessed [today's date]).

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