Is ARHGAP25 p.Pro246Ser (c.736C>T) pathogenic?

ARHGAP25 p.Pro246Ser (c.736C>T) is classified Uncertain significance in ARHGAP25 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). Absent from gnomAD v4.1.

How common is ARHGAP25 p.Pro246Ser (c.736C>T) in the general population?

ARHGAP25 p.Pro246Ser (c.736C>T) is absent from gnomAD v4.1 (gnomAD).

ARHGAP25 p.Pro246Ser

c.736C>T · rs2466648527 · VCV2560022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.694	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 91 kb · p 0.00048 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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: ARHGAP25
Protein: p.Pro246Ser
Coding: c.736C>T
MANE Select: NM_001007231
dbSNP: rs2466648527
Type: single nucleotide variant
Location: chr2:68813348 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.41 · 1 PDB
Residue 246: the rho-gap domain

Full ARHGAP25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP25 p.Ala101Thr Uncertain significance ★ same type
ARHGAP25 p.Ala265Val Uncertain significance ★ same type
ARHGAP25 p.Ala33Thr Uncertain significance ★ same type
ARHGAP25 p.Ala34Thr Uncertain significance ★ same type
ARHGAP25 p.Ala374Thr Uncertain significance ★ same type
ARHGAP25 p.Ala517Thr Uncertain significance ★ same type
ARHGAP25 p.Arg161His Uncertain significance ★ same type
ARHGAP25 p.Arg193Gln 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/arhgap25-p-pro246ser (accessed [today's date]).

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