Is AR p.Leu839= (c.2517C>T) pathogenic?

AR p.Leu839= (c.2517C>T) is classified Benign in AR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). Ultra-rare (popmax 0.0473%, nfe); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Leu839= (c.2517C>T)?

AR p.Leu839= (c.2517C>T) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Leu839= (c.2517C>T) in the general population?

AR p.Leu839= (c.2517C>T) is ultra-rare (popmax 0.0473%, nfe) (gnomAD).

AR p.Leu839=

c.2517C>T · rs6153 · VCV464799

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0473%, nfe)

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 -0.42	GERP -3.6, phastCons 0.15
Overall
CADD	0.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0473% European (non-Finnish) · 423/894,438 alleles

Filtering AF 0.0435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.037% 447/1,208,951 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0473%	2,115
Remaining individualsnot grpmax-eligible	0.0315%	3,173
Admixed American	0.0109%	9,147
African / African-American	0.00526%	19,028
Finnishnot grpmax-eligible	0.00215%	46,599

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.Leu839=
Coding: c.2517C>T
MANE Select: NM_000044
dbSNP: rs6153
Type: single nucleotide variant
Location: chrX:67722894 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 839: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; an α-helix; the 'interaction with lpxn' 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 p.Leu839Ile 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
AR p.Ala688Val Pathogenic/Likely pathogenic ★★ same condition
AR p.Ala766Thr 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-leu839 (accessed [today's date]).

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