Is AR p.Val3Met (c.7G>A) pathogenic?

AR p.Val3Met (c.7G>A) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-02-09). AlphaMissense: likely pathogenic (0.5717); Ultra-rare (popmax 0.0179%, eas); Associated with ovarian cancer.

What condition is associated with AR p.Val3Met (c.7G>A)?

AR p.Val3Met (c.7G>A) is associated with ovarian cancer, prostate cancer, hypospadias 1, X-linked (ClinVar).

How common is AR p.Val3Met (c.7G>A) in the general population?

AR p.Val3Met (c.7G>A) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about AR p.Val3Met (c.7G>A)?

AlphaMissense predicts likely pathogenic (score 0.5717) — an in-silico prediction, not a clinical call.

AR p.Val3Met

c.7G>A · rs778912582 · VCV1488550

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.5717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.5717	likely pathogenic
REVEL	0.58	indeterminate
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	25.7	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 0.0179% East Asian · 6/33,567 alleles

Filtering AF 0.0077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00529%

Overall 0.00142% 17/1,195,335 alleles · ultra-rare exomes 15/1,084,318 · genomes 2/111,017 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0235%	4,263
East Asiangrpmax	0.0179%	5,594

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val3Met
Coding: c.7G>A
MANE Select: NM_000044
dbSNP: rs778912582
Type: single nucleotide variant
Location: chrX:67545153 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 3: 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

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

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-val3met (accessed [today's date]).

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