Is AR p.Phe765= (c.2295C>T) pathogenic?

AR p.Phe765= (c.2295C>T) is classified Benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-28). Ultra-rare (popmax 0.0229%, mid); Associated with Kennedy disease.

What condition is associated with AR p.Phe765= (c.2295C>T)?

AR p.Phe765= (c.2295C>T) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Phe765= (c.2295C>T) in the general population?

AR p.Phe765= (c.2295C>T) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

How is Kennedy disease inherited?

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

AR p.Phe765=

c.2295C>T · rs369390411 · VCV2946277

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

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 -1.3	GERP -3.7, phastCons 0.002
Overall
CADD	1.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% Middle Eastern · 1/4,373 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000797%

Overall 0.00306% 37/1,211,043 alleles · ultra-rare exomes 36/1,098,145 · genomes 1/112,898 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0256%	3,899
Middle Easterngrpmax	0.0229%	4,373
Remaining individualsnot grpmax-eligible	0.0105%	9,521
East Asian	0.00592%	16,891
Admixed American	0.00218%	45,926
South Asian	0.00176%	56,872
European (non-Finnish)	0.00168%	59,699

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe765=
Coding: c.2295C>T
MANE Select: NM_000044
dbSNP: rs369390411
Type: single nucleotide variant
Location: chrX:67717599 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 765: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in ais); 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.Phe765Leu 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-phe765 (accessed [today's date]).

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