Is ARHGAP24 p.Ser415Arg (c.1245C>A) pathogenic?

ARHGAP24 p.Ser415Arg (c.1245C>A) is classified Uncertain significance in ARHGAP24 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-28). AlphaMissense: likely pathogenic (0.8967); Absent from gnomAD v4.1.

How common is ARHGAP24 p.Ser415Arg (c.1245C>A) in the general population?

ARHGAP24 p.Ser415Arg (c.1245C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP24 p.Ser415Arg (c.1245C>A)?

AlphaMissense predicts likely pathogenic (score 0.8967) — an in-silico prediction, not a clinical call.

ARHGAP24 p.Ser415Arg

c.1245C>A · rs747686314 · VCV2541720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8967 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8967	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP 3.5, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 430 kb · p 0.6 · regional, not allelic
Overall
CADD	18.11	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP24
Protein: p.Ser415Arg
Coding: c.1245C>A
MANE Select: NM_001025616
dbSNP: rs747686314
Type: single nucleotide variant
Location: chr4:85994899 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 415: a modified residue (phosphoserine); the 'disordered' region

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

Similar variants

ARHGAP24 p.Ser415Asn 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-ser415arg (accessed [today's date]).

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