Is AR p.Ala403Val (c.1208C>T) pathogenic?

AR p.Ala403Val (c.1208C>T) is classified Pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.1781); Rare (popmax 0.143%, eas); Associated with prostate cancer.

What condition is associated with AR p.Ala403Val (c.1208C>T)?

AR p.Ala403Val (c.1208C>T) is associated with prostate cancer (ClinVar).

How common is AR p.Ala403Val (c.1208C>T) in the general population?

AR p.Ala403Val (c.1208C>T) is rare (popmax 0.143%, eas) (gnomAD).

What do computational predictors say about AR p.Ala403Val (c.1208C>T)?

AlphaMissense predicts likely benign (score 0.1781) — an in-silico prediction, not a clinical call.

AR p.Ala403Val

c.1208C>T · rs772490323 · VCV1685537

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1781 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.143%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.1781	likely benign ⚠ discordant with ClinVar
REVEL	0.617	indeterminate
SaProt	LLR -9.85	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 5.8	GERP 2.1, phastCons 1
Overall
CADD	22.2	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 0.143% East Asian · 46/32,118 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0986%

Overall 0.00447% 53/1,184,788 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.143%	698
South Asian	0.00369%	27,110
Finnishnot grpmax-eligible	0.00233%	42,972
European (non-Finnish)	0.000453%	220,782

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.Ala403Val
Coding: c.1208C>T
MANE Select: NM_000044
dbSNP: rs772490323
Type: single nucleotide variant
Location: chrX:67546354 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 403: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

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

Similar variants

AR p.Val867Met Pathogenic ★★ ⚠ same condition
AR p.Gln63Leu Uncertain significance ★★ ⚠ same condition
AR p.Pro342Leu Uncertain significance ★★ ⚠ same condition
AR p.Ser176Arg Benign/Likely benign ★★ ⚠ same condition
AR p.Asn728Lys Pathogenic ★ ⚠ same condition
AR p.Gln70Ter Pathogenic ★ same condition
AR p.Trp399Arg Pathogenic ★ ⚠ same condition
AR c.1885+3718A>G Uncertain significance ★ 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-ala403val (accessed [today's date]).

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