Is RAB3GAP2 p.Ser548Arg (c.1644T>A) pathogenic?

RAB3GAP2 p.Ser548Arg (c.1644T>A) is classified Uncertain significance in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.9302); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with RAB3GAP2 p.Ser548Arg (c.1644T>A)?

RAB3GAP2 p.Ser548Arg (c.1644T>A) is associated with Inborn genetic diseases (ClinVar).

How common is RAB3GAP2 p.Ser548Arg (c.1644T>A) in the general population?

RAB3GAP2 p.Ser548Arg (c.1644T>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about RAB3GAP2 p.Ser548Arg (c.1644T>A)?

AlphaMissense predicts likely pathogenic (score 0.9302) — an in-silico prediction, not a clinical call.

RAB3GAP2 p.Ser548Arg

c.1644T>A · VCV4628766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9302	likely pathogenic · top 10% in RAB3GAP2
REVEL	0.145	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -2.7, phastCons 0.2
Regional constraint	o/e 0.99	unconstrained · MANE · 26 kb · p 0.76 · regional, not allelic
Overall
CADD	21.1	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 0.00667% Admixed American · 4/59,964 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000496% 8/1,612,458 alleles · very rare exomes 4/1,460,330 · genomes 4/152,128 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,991
Remaining individualsnot grpmax-eligible	0.0016%	62,428
European (non-Finnish)	0.000255%	392,918

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.Ser548Arg
Coding: c.1644T>A
MANE Select: NM_012414
Type: single nucleotide variant
Location: chr1:220190134 (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

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

Similar variants

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RAB3GAP2 p.Arg35Trp Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Arg415Lys Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn1188Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn697Ser Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asn960Asp Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Asp1114Asn Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Glu127Lys 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-ser548arg (accessed [today's date]).

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