Is ARHGAP23 p.Asp792Val (c.2375A>T) pathogenic?

ARHGAP23 p.Asp792Val (c.2375A>T) is classified Uncertain significance in ARHGAP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely pathogenic (0.9802); Absent from gnomAD v4.1.

How common is ARHGAP23 p.Asp792Val (c.2375A>T) in the general population?

ARHGAP23 p.Asp792Val (c.2375A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP23 p.Asp792Val (c.2375A>T)?

AlphaMissense predicts likely pathogenic (score 0.9802) — an in-silico prediction, not a clinical call.

ARHGAP23 p.Asp792Val

c.2375A>T · VCV4134536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9802 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9802	likely pathogenic · top 8% in ARHGAP23
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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: ARHGAP23
Protein: p.Asp792Val
Coding: c.2375A>T
MANE Select: NM_001199417
Type: single nucleotide variant
Location: chr17:38477835 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.82
Residue 792: the ph domain

Full ARHGAP23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP23 p.Ala1010Thr Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1010Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1153Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1222Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1324Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1340Thr Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1363Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1457Val 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/arhgap23-p-asp792val (accessed [today's date]).

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