Is ARHGAP32 p.Pro1420Ser (c.4258C>T) pathogenic?

ARHGAP32 p.Pro1420Ser (c.4258C>T) is classified Likely benign in ARHGAP32 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.0561); Very rare (popmax 0.000254%, nfe).

How common is ARHGAP32 p.Pro1420Ser (c.4258C>T) in the general population?

ARHGAP32 p.Pro1420Ser (c.4258C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ARHGAP32 p.Pro1420Ser (c.4258C>T)?

AlphaMissense predicts likely benign (score 0.0561) — an in-silico prediction, not a clinical call.

ARHGAP32 p.Pro1420Ser

c.4258C>T · VCV3891023

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0561	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.91	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 -0.76	GERP -5.2
Regional constraint	o/e 0.96	unconstrained · MANE · 5,700 bp · p 0.086 · regional, not allelic
Overall
CADD	0.052	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 P1406S vs ClinVar P1420S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,002 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,698 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.Pro1420Ser
Coding: c.4258C>T
MANE Select: NM_001378024
Type: single nucleotide variant
Location: chr11:128970955 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 43.67 · 2 PDB
Residue 1406 UniProt numbering: the 'interaction with gab2' region

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-pro1420ser (accessed [today's date]).

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