Is AR p.Ala871= (c.2613G>A) pathogenic?

AR p.Ala871= (c.2613G>A) is classified Benign/Likely benign in AR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-20). Ultra-rare (popmax 0.0233%, mid); Associated with Kennedy disease.

What condition is associated with AR p.Ala871= (c.2613G>A)?

AR p.Ala871= (c.2613G>A) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Ala871= (c.2613G>A) in the general population?

AR p.Ala871= (c.2613G>A) is ultra-rare (popmax 0.0233%, mid) (gnomAD).

How is Kennedy disease inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AR p.Ala871=

c.2613G>A · rs780838814 · VCV2943082

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, mid)

Conditions

Kennedy disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.252	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -3.7, phastCons 0.98
Overall
CADD	4.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Middle Eastern · 1/4,292 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000729% 8/1,097,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0233%	4,292
South Asian	0.00352%	28,449
European (non-Finnish)	0.000559%	179,029

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.Ala871=
Coding: c.2613G>A
MANE Select: NM_000044
dbSNP: rs780838814
Type: single nucleotide variant
Location: chrX:67723691 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 871: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in pais); an α-helix; the 'interaction with lpxn' region

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

Disease context

Kennedy disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: androgen insensitivity syndrome

For Kennedy disease (Orphanet):

Inheritance: X-linked recessive
Onset: Adult
Prevalence: <1 / 1 000 000 (Italy)

Similar variants

AR p.Ala871Val Pathogenic/Likely pathogenic ★★ same residue
AR p.Ala871Glu Pathogenic ★ ⚠ same residue
AR p.Ala871Gly Likely pathogenic ★ ⚠ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same condition
AR c.1769-11T>A Pathogenic ★★ same condition
AR c.2450-6C>G Pathogenic ★★ same condition
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same condition
AR p.Ala597Thr 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-ala871 (accessed [today's date]).

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