Is AR p.Arg9= (c.27G>A) pathogenic?

AR p.Arg9= (c.27G>A) is classified Likely benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-29). Very rare (popmax 0.00533%, afr); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Arg9= (c.27G>A)?

AR p.Arg9= (c.27G>A) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Arg9= (c.27G>A) in the general population?

AR p.Arg9= (c.27G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

AR p.Arg9=

c.27G>A · VCV4790729

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Conditions

androgen insensitivity syndrome

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 4.7	GERP 0.25, phastCons 1
Overall
CADD	12.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 3/56,324 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000692%

Overall 0.000333% 4/1,200,307 alleles · very rare exomes 2/1,089,707 · genomes 2/110,600 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,775
European (non-Finnish)	0.000112%	891,870

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: AR
Protein: p.Arg9=
Coding: c.27G>A
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67545173 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 9: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

androgen insensitivity syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Kennedy disease

Similar variants

AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same condition
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AR c.2450-6C>G Pathogenic ★★ same condition
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same condition
AR p.Ala597Thr Pathogenic ★★ same condition
AR p.Ala688Val Pathogenic/Likely pathogenic ★★ same condition
AR p.Ala766Thr Pathogenic ★★ same condition
AR p.Ala871Val Pathogenic/Likely pathogenic ★★ 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/ar-p-arg9 (accessed [today's date]).

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