Is AR p.Leu295= (c.885A>C) pathogenic?

AR p.Leu295= (c.885A>C) is classified Likely benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). Absent from gnomAD v4.1; Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Leu295= (c.885A>C)?

AR p.Leu295= (c.885A>C) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Leu295= (c.885A>C) in the general population?

AR p.Leu295= (c.885A>C) is absent from gnomAD v4.1 (gnomAD).

AR p.Leu295=

c.885A>C · VCV4784906

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 4.9	GERP -0.83, phastCons 1
Overall
CADD	6.278	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AR
Protein: p.Leu295=
Coding: c.885A>C
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67546031 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 295: 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 p.Leu295Pro Uncertain significance ★ ⚠ 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-leu295 (accessed [today's date]).

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