Is ARHGAP26 p.Arg85= (c.255A>G) pathogenic?

ARHGAP26 p.Arg85= (c.255A>G) is classified Benign in ARHGAP26 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 86%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ARHGAP26-related disorder.

What condition is associated with ARHGAP26 p.Arg85= (c.255A>G)?

ARHGAP26 p.Arg85= (c.255A>G) is associated with ARHGAP26-related disorder (ClinVar).

ARHGAP26 p.Arg85=

Q: How common is ARHGAP26 p.Arg85= (c.255A>G) in the general population?

ARHGAP26 p.Arg85= (c.255A>G) is common (popmax 86%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.255A>G · rs185200 · VCV3059213

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 86%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

ARHGAP26-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -1.2, phastCons 1
Overall
CADD	10.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 86% East Asian · 38,573/44,864 alleles

Filtering AF 85.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 85%

Overall 36.2% 584,090/1,612,584 alleles · common exomes 511,089/1,460,516 · genomes 73,001/152,068 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	86%	1
African / African-American	80.2%	1
South Asian	60.7%	2
Admixed American	51.7%	2
Middle Eastern	42.7%	2
Remaining individualsnot grpmax-eligible	39.9%	3
Ashkenazi Jewishnot grpmax-eligible	32.5%	3
Amishnot grpmax-eligible	31.1%	3
Finnishnot grpmax-eligible	29.8%	3
European (non-Finnish)	29.1%	3

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: ARHGAP26
Protein: p.Arg85=
Coding: c.255A>G
MANE Select: NM_001135608
dbSNP: rs185200
Type: single nucleotide variant
Location: chr5:142875114 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.09 · 1 PDB
Residue 85: the bar domain

Full ARHGAP26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARHGAP26-related disorder

Similar variants

ARHGAP26 c.1285+9C>T Likely benign same condition
ARHGAP26 c.154+462T>C Benign same condition
ARHGAP26 c.1838-10T>C Likely benign same condition
ARHGAP26 c.486+7G>A Likely benign same condition
ARHGAP26 p.Asn730= Benign same condition
ARHGAP26 p.Asp649= Likely benign same condition
ARHGAP26 p.Gly415= Benign same condition
ARHGAP26 p.His564= Likely benign same condition

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/arhgap26-p-arg85 (accessed [today's date]).

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