Is ARHGAP25 p.Pro355= (c.1065C>G) pathogenic?

ARHGAP25 p.Pro355= (c.1065C>G) is classified Likely benign in ARHGAP25 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-03). Rare (popmax 0.252%, nfe); Associated with ARHGAP25-related condition.

What condition is associated with ARHGAP25 p.Pro355= (c.1065C>G)?

ARHGAP25 p.Pro355= (c.1065C>G) is associated with ARHGAP25-related condition (ClinVar).

How common is ARHGAP25 p.Pro355= (c.1065C>G) in the general population?

ARHGAP25 p.Pro355= (c.1065C>G) is rare (popmax 0.252%, nfe) (gnomAD).

ARHGAP25 p.Pro355=

c.1065C>G · VCV3350491

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.252%, nfe)

Conditions

ARHGAP25-related condition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.124	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP 1, phastCons 0.98
Overall
CADD	8.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.252% European (non-Finnish) · 2,968/1,176,724 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.242%

Overall 0.206% 3,307/1,607,962 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.252%	396
Middle Eastern	0.25%	400
Remaining individualsnot grpmax-eligible	0.238%	420
Admixed American	0.184%	543
African / African-American	0.0402%	2,490
Finnishnot grpmax-eligible	0.0297%	3,362
Ashkenazi Jewishnot grpmax-eligible	0.0275%	3,637
South Asian	0.0111%	9,047

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: ARHGAP25
Protein: p.Pro355=
Coding: c.1065C>G
MANE Select: NM_001007231
Type: single nucleotide variant
Location: chr2:68819184 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.41 · 1 PDB
Residue 355: the 'disordered' region

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

Disease context

ARHGAP25-related condition

Similar variants

ARHGAP25 p.Glu254Lys Likely benign same condition
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

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-pro355 (accessed [today's date]).

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