Is AR p.Leu763= (c.2289C>G) pathogenic?

AR p.Leu763= (c.2289C>G) is classified Likely benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-16). Very rare (popmax 0.00123%, nfe); Associated with Kennedy disease.

What condition is associated with AR p.Leu763= (c.2289C>G)?

AR p.Leu763= (c.2289C>G) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Leu763= (c.2289C>G) in the general population?

AR p.Leu763= (c.2289C>G) is very rare (popmax 0.00123%, nfe) (gnomAD).

How is Kennedy disease inherited?

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

AR p.Leu763=

c.2289C>G · rs2147531084 · VCV2943262

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00123%, nfe)

Conditions

Kennedy disease

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 0.12	GERP -1.4, phastCons 0.95
Overall
CADD	7.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00123% European (non-Finnish) · 11/895,626 alleles

Filtering AF 0.000659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000482%

Overall 0.001% 11/1,098,151 alleles · very rare

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.Leu763=
Coding: c.2289C>G
MANE Select: NM_000044
dbSNP: rs2147531084
Type: single nucleotide variant
Location: chrX:67717593 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 763: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in ais; loss of androgen binding); a β-strand; 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.Leu763Val 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
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-leu763 (accessed [today's date]).

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