Is ARHGAP23 p.Trp1403Gly (c.4207T>G) pathogenic?

ARHGAP23 p.Trp1403Gly (c.4207T>G) is classified Uncertain significance in ARHGAP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely pathogenic (0.8773); Absent from gnomAD v4.1.

How common is ARHGAP23 p.Trp1403Gly (c.4207T>G) in the general population?

ARHGAP23 p.Trp1403Gly (c.4207T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP23 p.Trp1403Gly (c.4207T>G)?

AlphaMissense predicts likely pathogenic (score 0.8773) — an in-silico prediction, not a clinical call.

ARHGAP23 p.Trp1403Gly

c.4207T>G · rs1344337594 · VCV2229633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8773 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8773	likely pathogenic
REVEL	0.07	moderately benign-leaning
SaProt	LLR -3.69	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.65, phastCons 1
Overall
CADD	24.8	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

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.Trp1403Gly
Coding: c.4207T>G
MANE Select: NM_001199417
dbSNP: rs1344337594
Type: single nucleotide variant
Location: chr17:38510703 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.82

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

Similar variants

ARHGAP23 p.Trp1403Arg Uncertain significance ★ ⚠ same residue
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

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-trp1403gly (accessed [today's date]).

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