Is ARHGAP24 p.Ala235Val (c.704C>T) pathogenic?

ARHGAP24 p.Ala235Val (c.704C>T) is classified Uncertain significance in ARHGAP24 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: ambiguous (0.5484); Ultra-rare (popmax 0.0549%, sas).

How common is ARHGAP24 p.Ala235Val (c.704C>T) in the general population?

ARHGAP24 p.Ala235Val (c.704C>T) is ultra-rare (popmax 0.0549%, sas) (gnomAD).

What do computational predictors say about ARHGAP24 p.Ala235Val (c.704C>T)?

AlphaMissense predicts ambiguous (score 0.5484) — an in-silico prediction, not a clinical call.

ARHGAP24 p.Ala235Val

c.704C>T · rs760970265 · VCV3128669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5484 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5484	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -8.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 4.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 430 kb · p 0.6 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.0549% South Asian · 50/91,034 alleles

Filtering AF 0.0427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0044% 71/1,613,408 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0549%	1,821
Admixed American	0.015%	6,659
Remaining individualsnot grpmax-eligible	0.008%	12,496
East Asian	0.00223%	44,866
African / African-American	0.00134%	74,734
European (non-Finnish)	0.000424%	235,992

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: ARHGAP24
Protein: p.Ala235Val
Coding: c.704C>T
MANE Select: NM_001025616
dbSNP: rs760970265
Type: single nucleotide variant
Location: chr4:85972140 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 235: the rho-gap domain

Full ARHGAP24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP24 p.Arg39His Uncertain significance ★★ ⚠ same type
ARHGAP24 p.Arg483Cys Uncertain significance ★★ ⚠ same type
ARHGAP24 p.Arg93Ter Uncertain significance ★★ same type
ARHGAP24 p.Arg95Gln Uncertain significance ★★ ⚠ same type
ARHGAP24 p.Asn454Ser Uncertain significance ★★ ⚠ same type
ARHGAP24 p.Asn587Ile Uncertain significance ★★ ⚠ same type
ARHGAP24 p.Asp55Val Uncertain significance ★★ ⚠ same type
ARHGAP24 p.Gln158Arg 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/arhgap24-p-ala235val (accessed [today's date]).

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