Is ARHGAP24 p.Asp139Val (c.416A>T) pathogenic?

ARHGAP24 p.Asp139Val (c.416A>T) is classified Benign in ARHGAP24 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.6534); Ultra-rare (popmax 0.0167%, mid).

How common is ARHGAP24 p.Asp139Val (c.416A>T) in the general population?

ARHGAP24 p.Asp139Val (c.416A>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ARHGAP24 p.Asp139Val (c.416A>T)?

AlphaMissense predicts likely pathogenic (score 0.6534) — an in-silico prediction, not a clinical call.

ARHGAP24 p.Asp139Val

c.416A>T · rs149943050 · VCV2064948

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6534 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6534	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -10.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 430 kb · p 0.6 · regional, not allelic
Overall
CADD	26.2	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 0.0167% Middle Eastern · 1/5,978 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.0272% 439/1,613,652 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.09%	92
Remaining individualsnot grpmax-eligible	0.0865%	1,157
Middle Easterngrpmax	0.0167%	5,978
European (non-Finnish)	0.00508%	19,666
South Asian	0.0022%	45,532

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp139Val
Coding: c.416A>T
MANE Select: NM_001025616
dbSNP: rs149943050
Type: single nucleotide variant
Location: chr4:85942090 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 139: 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-asp139val (accessed [today's date]).

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