Is ARHGAP32 p.Ser752Phe (c.2255C>T) pathogenic?

ARHGAP32 p.Ser752Phe (c.2255C>T) is classified Uncertain significance in ARHGAP32 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely pathogenic (0.8049); Very rare (popmax 0.01%, amr).

How common is ARHGAP32 p.Ser752Phe (c.2255C>T) in the general population?

ARHGAP32 p.Ser752Phe (c.2255C>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about ARHGAP32 p.Ser752Phe (c.2255C>T)?

AlphaMissense predicts likely pathogenic (score 0.8049) — an in-silico prediction, not a clinical call.

ARHGAP32 p.Ser752Phe

c.2255C>T · VCV3940367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8049	likely pathogenic
REVEL	0.344	indeterminate
SaProt	LLR -7.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 6,800 bp · p 0.00076 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S738F vs ClinVar S752F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,006 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00041% 6/1,461,636 alleles · very rare

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: ARHGAP32
Protein: p.Ser752Phe
Coding: c.2255C>T
MANE Select: NM_001378024
Type: single nucleotide variant
Location: chr11:128974942 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 43.67 · 2 PDB

Full ARHGAP32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP32 c.360-10T>C Benign/Likely benign ★★ same type
ARHGAP32 p.Ala1413= Benign ★★ same type
ARHGAP32 p.Ala2078= Likely benign ★★ same type
ARHGAP32 p.Arg1412= Benign ★★ same type
ARHGAP32 p.Arg1629= Likely benign ★★ same type
ARHGAP32 p.Arg1726Trp Benign ★★ same type
ARHGAP32 p.Glu1154Gly Benign ★★ same type
ARHGAP32 p.Glu390= Benign ★★ 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/arhgap32-p-ser752phe (accessed [today's date]).

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