Is ARHGAP24 p.Phe633Ser (c.1898T>C) pathogenic?

ARHGAP24 p.Phe633Ser (c.1898T>C) is classified Uncertain significance in ARHGAP24 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-17). AlphaMissense: likely benign (0.3139); Very rare (popmax 0.00848%, nfe).

How common is ARHGAP24 p.Phe633Ser (c.1898T>C) in the general population?

ARHGAP24 p.Phe633Ser (c.1898T>C) is very rare (popmax 0.00848%, nfe) (gnomAD).

What do computational predictors say about ARHGAP24 p.Phe633Ser (c.1898T>C)?

AlphaMissense predicts likely benign (score 0.3139) — an in-silico prediction, not a clinical call.

ARHGAP24 p.Phe633Ser

c.1898T>C · rs749403214 · VCV3128664

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00848%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3139	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -3.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 7.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 430 kb · p 0.6 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00848% European (non-Finnish) · 100/1,178,868 alleles

Filtering AF 0.00708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0066%

Overall 0.00645% 104/1,612,132 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00848%	11,789
Remaining individualsnot grpmax-eligible	0.0032%	31,215
African / African-American	0.00267%	37,420

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.Phe633Ser
Coding: c.1898T>C
MANE Select: NM_001025616
dbSNP: rs749403214
Type: single nucleotide variant
Location: chr4:85995552 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 633: the 'disordered' region

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

Similar variants

ARHGAP24 p.Phe633= 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.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-phe633ser (accessed [today's date]).

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