Is ARHGAP12 p.Val482Phe (c.1444G>T) pathogenic?

ARHGAP12 p.Val482Phe (c.1444G>T) is classified Uncertain significance in ARHGAP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.7425); Very rare (popmax 0.00945%, afr).

How common is ARHGAP12 p.Val482Phe (c.1444G>T) in the general population?

ARHGAP12 p.Val482Phe (c.1444G>T) is very rare (popmax 0.00945%, afr) (gnomAD).

What do computational predictors say about ARHGAP12 p.Val482Phe (c.1444G>T)?

AlphaMissense predicts likely pathogenic (score 0.7425) — an in-silico prediction, not a clinical call.

ARHGAP12 p.Val482Phe

c.1444G>T · VCV4133129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00945%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7425	likely pathogenic
REVEL	0.281	benign-leaning
SaProt	LLR -13.08	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 4	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 101 kb · p 0.038 · regional, not allelic
Overall
CADD	24.9	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 0.00945% African / African-American · 7/74,072 alleles

Filtering AF 0.00442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.0021% 33/1,575,048 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00945%	10,582
Remaining individualsnot grpmax-eligible	0.00327%	30,536
East Asian	0.00227%	44,076
South Asian	0.00225%	44,429
European (non-Finnish)	0.00174%	57,407
Admixed American	0.0017%	58,996

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: ARHGAP12
Protein: p.Val482Phe
Coding: c.1444G>T
MANE Select: NM_018287
Type: single nucleotide variant
Location: chr10:31831743 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.68
Residue 482: the ph domain

Full ARHGAP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP12 p.Arg6= Benign ★★ same type
ARHGAP12 p.Ala393Val Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala458Ser Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala458Val Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala491Ser Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala491Val Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala698Thr Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala753Ser 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/arhgap12-p-val482phe (accessed [today's date]).

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