Is AR p.Pro97Ser (c.289C>T) pathogenic?

AR p.Pro97Ser (c.289C>T) is classified Benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.0751); Very rare (popmax 0.00903%, eas); Associated with ovarian cancer.

What condition is associated with AR p.Pro97Ser (c.289C>T)?

AR p.Pro97Ser (c.289C>T) is associated with ovarian cancer (ClinVar).

How common is AR p.Pro97Ser (c.289C>T) in the general population?

AR p.Pro97Ser (c.289C>T) is very rare (popmax 0.00903%, eas) (gnomAD).

What do computational predictors say about AR p.Pro97Ser (c.289C>T)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

AR p.Pro97Ser

c.289C>T · rs1329298379 · VCV2445345

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00903%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.539	indeterminate
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP 0.68, phastCons 0.96
Overall
CADD	13.85	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 0.00903% East Asian · 3/33,235 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.00025% 3/1,200,491 alleles · very rare exomes 3/1,088,445 · genomes 0/112,046 · joint denominator

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.Pro97Ser
Coding: c.289C>T
MANE Select: NM_000044
dbSNP: rs1329298379
Type: single nucleotide variant
Location: chrX:67545435 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 97: 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

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

Similar variants

AR p.Pro97= Likely benign ★ 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-pro97ser (accessed [today's date]).

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