Is ARHGAP24 p.Asp55Val (c.164A>T) pathogenic?

ARHGAP24 p.Asp55Val (c.164A>T) is classified Uncertain significance in ARHGAP24 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). AlphaMissense: ambiguous (0.3936); Ultra-rare (popmax 0.0183%, amr).

How common is ARHGAP24 p.Asp55Val (c.164A>T) in the general population?

ARHGAP24 p.Asp55Val (c.164A>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about ARHGAP24 p.Asp55Val (c.164A>T)?

AlphaMissense predicts ambiguous (score 0.3936) — an in-silico prediction, not a clinical call.

ARHGAP24 p.Asp55Val

c.164A>T · rs139936589 · VCV2355844

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Computational evidence

Protein change
AlphaMissense	0.3936	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -8.27	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 430 kb · p 0.6 · regional, not allelic
Overall
CADD	26.0	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 0.0183% Admixed American · 11/60,004 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00285% 46/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00271%	36,875
African / African-American	0.00267%	37,456

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.Asp55Val
Coding: c.164A>T
MANE Select: NM_001025616
dbSNP: rs139936589
Type: single nucleotide variant
Location: chr4:85570705 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 55: the ph domain

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

Similar variants

ARHGAP24 p.Asp55= Likely benign ★★ same residue
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.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-asp55val (accessed [today's date]).

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