Is ARHGAP24 p.Tyr147= (c.441T>C) pathogenic?

ARHGAP24 p.Tyr147= (c.441T>C) is classified Likely benign in ARHGAP24 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). Very rare (popmax 0.00167%, amr).

How common is ARHGAP24 p.Tyr147= (c.441T>C) in the general population?

ARHGAP24 p.Tyr147= (c.441T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

ARHGAP24 p.Tyr147=

c.441T>C · rs772914890 · VCV1920319

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -4.3
Overall
CADD	1.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,980 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,854 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,235
Admixed Americangrpmax	0.00167%	59,980
European (non-Finnish)	0.000593%	168,571

Remaining individuals 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.Tyr147=
Coding: c.441T>C
MANE Select: NM_001025616
dbSNP: rs772914890
Type: single nucleotide variant
Location: chr4:85942115 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 147: the rho-gap domain

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

Similar variants

ARHGAP24 p.Tyr147Cys Uncertain significance ★ ⚠ 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.Asp55Val 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-tyr147 (accessed [today's date]).

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