Is AR p.Val512= (c.1536G>A) pathogenic?

AR p.Val512= (c.1536G>A) is classified Benign/Likely benign in AR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-08). Ultra-rare (popmax 0.0968%, nfe); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Val512= (c.1536G>A)?

AR p.Val512= (c.1536G>A) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Val512= (c.1536G>A) in the general population?

AR p.Val512= (c.1536G>A) is ultra-rare (popmax 0.0968%, nfe) (gnomAD).

AR p.Val512=

c.1536G>A · rs150545747 · VCV464790

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0968%, nfe)

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 1.3	GERP -1.8, phastCons 1
Overall
CADD	10.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0968% European (non-Finnish) · 865/893,539 alleles

Filtering AF 0.0914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0893%

Overall 0.074% 893/1,206,231 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0968%	1,033
Remaining individualsnot grpmax-eligible	0.0316%	3,166
Finnishnot grpmax-eligible	0.0173%	5,773
African / African-American	0.00702%	14,246
Admixed American	0.0022%	45,494

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.Val512=
Coding: c.1536G>A
MANE Select: NM_000044
dbSNP: rs150545747
Type: single nucleotide variant
Location: chrX:67546682 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 512: 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 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
AR p.Ala871Val Pathogenic/Likely 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-val512 (accessed [today's date]).

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