Is AR p.Gln63Leu (c.188A>T) pathogenic?

AR p.Gln63Leu (c.188A>T) is classified Uncertain significance in AR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-08-25). AlphaMissense: likely benign (0.1422); Ultra-rare (popmax 0.0122%, afr); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Gln63Leu (c.188A>T)?

AR p.Gln63Leu (c.188A>T) is associated with androgen insensitivity syndrome, prostate cancer, Kennedy disease (ClinVar).

How common is AR p.Gln63Leu (c.188A>T) in the general population?

AR p.Gln63Leu (c.188A>T) is ultra-rare (popmax 0.0122%, afr) (gnomAD).

What do computational predictors say about AR p.Gln63Leu (c.188A>T)?

AlphaMissense predicts likely benign (score 0.1422) — an in-silico prediction, not a clinical call.

AR p.Gln63Leu

c.188A>T · rs62636527 · VCV931831

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1422 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.1422	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -11.38	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP 0.63, phastCons 0.99
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0122% African / African-American · 5/40,979 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000842% 9/1,069,007 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0122%	8,196
Remaining individualsnot grpmax-eligible	0.00238%	42,065
European (non-Finnish)	0.000371%	269,674

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.Gln63Leu
Coding: c.188A>T
MANE Select: NM_000044
dbSNP: rs62636527
Type: single nucleotide variant
Location: chrX:67545334 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 63: the 'interaction with znf318' region; the 'modulating' region; the 'disordered' 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: prostate cancer Kennedy disease

Similar variants

AR p.Gln63Ter 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-gln63leu (accessed [today's date]).

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