Is AR p.Ala253Val (c.758C>T) pathogenic?

AR p.Ala253Val (c.758C>T) is classified Benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.1125); Very rare (popmax 0.00524%, afr); Associated with ovarian cancer.

What condition is associated with AR p.Ala253Val (c.758C>T)?

AR p.Ala253Val (c.758C>T) is associated with ovarian cancer (ClinVar).

How common is AR p.Ala253Val (c.758C>T) in the general population?

AR p.Ala253Val (c.758C>T) is very rare (popmax 0.00524%, afr) (gnomAD).

What do computational predictors say about AR p.Ala253Val (c.758C>T)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

AR p.Ala253Val

c.758C>T · rs769445750 · VCV2445408

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00524%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.701	pathogenic-leaning
SaProt	LLR -7.34	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 3.2	GERP 2, phastCons 1
Overall
CADD	23.4	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 0.00524% African / African-American · 3/57,302 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000685%

Overall 0.00033% 4/1,210,424 alleles · very rare exomes 2/1,098,107 · genomes 2/112,317 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00524%	19,101
South Asian	0.00176%	56,861

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.Ala253Val
Coding: c.758C>T
MANE Select: NM_000044
dbSNP: rs769445750
Type: single nucleotide variant
Location: chrX:67545904 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 253: the 'interaction with znf318' region; the 'modulating' region

Full AR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.Ala253Gly Uncertain significance ★ ⚠ same residue
AR p.Leu57Gln Benign/Likely benign ★★ same condition
AR p.Ser495Asn Benign ★★ same condition
AR p.Ala736Asp Likely pathogenic ★ ⚠ same condition
AR p.Arg386Leu Likely pathogenic ★ ⚠ same condition
AR p.Glu474Gly Likely pathogenic ★ ⚠ same condition
AR p.Gly454Arg Likely pathogenic ★ ⚠ same condition
AR p.Gly396Arg Conflicting classifications of pathogenicity ★ ⚠ 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-ala253val (accessed [today's date]).

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