Is ARHGAP5 p.Val418= (c.1254A>G) pathogenic?

ARHGAP5 p.Val418= (c.1254A>G) is classified Benign in ARHGAP5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-18). Common (popmax 5.6%, afr) — too common for a highly-penetrant pathogenic allele.

ARHGAP5 p.Val418=

Q: How common is ARHGAP5 p.Val418= (c.1254A>G) in the general population?

ARHGAP5 p.Val418= (c.1254A>G) is common (popmax 5.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1254A>G · rs61747596 · VCV786247

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.6%, afr) — too common for a highly-penetrant pathogenic allele

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 0.53	GERP 2, phastCons 0.83
Overall
CADD	4.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.6% African / African-American · 4,202/75,008 alleles

Filtering AF 5.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4%

Overall 0.314% 5,061/1,613,700 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.6%	18
Remaining individualsnot grpmax-eligible	0.528%	189
Admixed American	0.46%	217
Ashkenazi Jewishnot grpmax-eligible	0.399%	251
Middle Eastern	0.247%	404
European (non-Finnish)	0.00949%	10,533
South Asian	0.00659%	15,176
East Asian	0.00446%	22,435

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: ARHGAP5
Protein: p.Val418=
Coding: c.1254A>G
MANE Select: NM_001030055
dbSNP: rs61747596
Type: single nucleotide variant
Location: chr14:32091923 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.37 · 3 PDB
Residue 418: the ff 2 domain

Full ARHGAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP5 p.Arg1193Cys Uncertain significance ★★ ⚠ same type
ARHGAP5 p.Asn953Ser Benign ★★ same type
ARHGAP5 p.Asp971= Benign ★★ same type
ARHGAP5 p.Gln726= Benign ★★ same type
ARHGAP5 p.Leu342= Benign ★★ same type
ARHGAP5 p.Pro768= Benign ★★ same type
ARHGAP5 p.Ala1064Val Uncertain significance ★ ⚠ same type
ARHGAP5 p.Ala1092Val 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/arhgap5-p-val418 (accessed [today's date]).

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