Is ARHGAP32 p.Pro1620Ser (c.4858C>T) pathogenic?

ARHGAP32 p.Pro1620Ser (c.4858C>T) is classified Uncertain significance in ARHGAP32 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: ambiguous (0.4875); Absent from gnomAD v4.1.

How common is ARHGAP32 p.Pro1620Ser (c.4858C>T) in the general population?

ARHGAP32 p.Pro1620Ser (c.4858C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP32 p.Pro1620Ser (c.4858C>T)?

AlphaMissense predicts ambiguous (score 0.4875) — an in-silico prediction, not a clinical call.

ARHGAP32 p.Pro1620Ser

c.4858C>T · rs2497871997 · VCV2257354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4875	ambiguous
REVEL	0.293	indeterminate
SaProt	LLR -5.96	tolerated
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 0.96	unconstrained · MANE · 5,700 bp · p 0.086 · regional, not allelic
Overall
CADD	26.5	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 P1606S vs ClinVar P1620S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP32
Protein: p.Pro1620Ser
Coding: c.4858C>T
MANE Select: NM_001378024
dbSNP: rs2497871997
Type: single nucleotide variant
Location: chr11:128970355 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 43.67 · 2 PDB
Residue 1606 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-pro1620ser (accessed [today's date]).

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