Is RAB3GAP1 p.Ser73Ala (c.217T>G) pathogenic?

RAB3GAP1 p.Ser73Ala (c.217T>G) is classified Uncertain significance in RAB3GAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-13). AlphaMissense: likely benign (0.0673); Rare (popmax 0.112%, afr); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP1 p.Ser73Ala (c.217T>G)?

RAB3GAP1 p.Ser73Ala (c.217T>G) is associated with Inborn genetic diseases (ClinVar).

How common is RAB3GAP1 p.Ser73Ala (c.217T>G) in the general population?

RAB3GAP1 p.Ser73Ala (c.217T>G) is rare (popmax 0.112%, afr) (gnomAD).

What do computational predictors say about RAB3GAP1 p.Ser73Ala (c.217T>G)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

RAB3GAP1 p.Ser73Ala

c.217T>G · rs372673436 · VCV436463

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.35, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 82 kb · p 0.34 · regional, not allelic
Overall
CADD	16.79	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 0.112% African / African-American · 84/74,854 alleles

Filtering AF 0.0928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0857%

Overall 0.00548% 88/1,606,870 alleles · rare exomes 43/1,454,600 · genomes 45/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	891
Remaining individualsnot grpmax-eligible	0.00642%	15,564

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.Ser73Ala
Coding: c.217T>G
MANE Select: NM_012233
dbSNP: rs372673436
Type: single nucleotide variant
Location: chr2:135091064 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.46 · 1 PDB
Residue 73: a β-strand

Full RAB3GAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB3GAP1 p.Ser73= Likely benign ★ same residue
RAB3GAP1 c.748+1G>A Pathogenic ★★ same condition
RAB3GAP1 p.Arg347Ter Pathogenic ★★ same condition
RAB3GAP1 p.Ala538Val Uncertain significance ★★ ⚠ same condition
RAB3GAP1 p.Arg125Cys Uncertain significance ★★ ⚠ same condition
RAB3GAP1 p.Arg174Gln Uncertain significance ★★ ⚠ same condition
RAB3GAP1 p.Arg315Gln Uncertain significance ★★ ⚠ same condition
RAB3GAP1 p.Arg530Cys 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/rab3gap1-p-ser73ala (accessed [today's date]).

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