Is AR p.Val867Met (c.2599G>A) pathogenic?

AR p.Val867Met (c.2599G>A) is classified Pathogenic in AR (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-03-05). AlphaMissense: ambiguous (0.5068); Very rare (popmax 9.11e-05%); Associated with AR-related disorders.

What condition is associated with AR p.Val867Met (c.2599G>A)?

AR p.Val867Met (c.2599G>A) is associated with AR-related disorders, prostate cancer, hypospadias 1, X-linked (ClinVar).

How common is AR p.Val867Met (c.2599G>A) in the general population?

AR p.Val867Met (c.2599G>A) is very rare (popmax 9.11e-05%) (gnomAD).

What do computational predictors say about AR p.Val867Met (c.2599G>A)?

AlphaMissense predicts ambiguous (score 0.5068) — an in-silico prediction, not a clinical call.

AR p.Val867Met

c.2599G>A · rs137852564 · VCV9806

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.5068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

AR-related disorders

Computational evidence

Protein change
AlphaMissense	0.5068	ambiguous
REVEL	0.644	pathogenic-leaning
SaProt	LLR -7.71	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, 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 9.11e-05%

Overall 9.11e-05% 1/1,098,026 alleles · very rare

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.Val867Met
Coding: c.2599G>A
MANE Select: NM_024417 · reported on NM_000044
dbSNP: rs137852564
Type: single nucleotide variant
Location: chrX:67722976 (GRCh38)
Structure: AlphaFold pLDDT 91.66

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

Disease context

AR-related disorders

Also linked: prostate cancer hypospadias 1, X-linked partial androgen insensitivity syndrome Kennedy disease androgen insensitivity syndrome

Similar variants

AR p.Val867Leu Pathogenic ⚠ 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-val867met (accessed [today's date]).

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