Is AR p.Pro505Thr (c.1513C>A) pathogenic?

AR p.Pro505Thr (c.1513C>A) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-04). AlphaMissense: likely benign (0.2611); Ultra-rare (popmax 0.023%, mid); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Pro505Thr (c.1513C>A)?

AR p.Pro505Thr (c.1513C>A) is associated with androgen insensitivity syndrome, male infertility, Kennedy disease (ClinVar).

How common is AR p.Pro505Thr (c.1513C>A) in the general population?

AR p.Pro505Thr (c.1513C>A) is ultra-rare (popmax 0.023%, mid) (gnomAD).

What do computational predictors say about AR p.Pro505Thr (c.1513C>A)?

AlphaMissense predicts likely benign (score 0.2611) — an in-silico prediction, not a clinical call.

AR p.Pro505Thr

c.1513C>A · rs764238988 · VCV522694

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2611 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.2611	likely benign
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -7.55	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.2, phastCons 1
Overall
CADD	23.9	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 0.023% Middle Eastern · 1/4,344 alleles

Filtering AF 0.00708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.00457% 55/1,203,937 alleles · ultra-rare exomes 51/1,093,383 · genomes 4/110,554 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,344
South Asian	0.0144%	6,936
Remaining individualsnot grpmax-eligible	0.00633%	15,799
European (non-Finnish)	0.00482%	20,754

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.Pro505Thr
Coding: c.1513C>A
MANE Select: NM_000044
dbSNP: rs764238988
Type: single nucleotide variant
Location: chrX:67546659 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 505: 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: male infertility Kennedy disease

Similar variants

AR p.Pro505= Likely benign ★ 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-pro505thr (accessed [today's date]).

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