AMH p.Val477Ala
c.1430T>C · VCV3896650
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8828 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
persistent Mullerian duct syndrome
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8828 | likely pathogenic ✓ concordant with ClinVar · top 8% in AMH |
|---|---|---|
| REVEL | 0.649 | pathogenic-leaning |
| SaProt | LLR -10.49 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1, phastCons 1 |
| Regional constraint | o/e 1.27 | unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic |
| Overall | ||
| CADD | 25.4 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AMH
- Protein
- p.Val477Ala
- Coding
- c.1430T>C
- MANE Select
- NM_000479
- Type
- single nucleotide variant
- Location
- chr19:2251704 (GRCh38)
- Gene constraint
- LOEUF 1.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 69.40 · 3 PDB
- Residue 477
- a disulfide bond; a UniProt-annotated variant site (in pmds1); a β-strand; the 'binding to amh prodomain' region
Similar variants
- AMH p.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
- AMH p.Gln217Ter Pathogenic/Likely pathogenic ★★ same condition
- AMH p.Glu389Ter Pathogenic/Likely pathogenic ★★ same condition
- AMH p.Gly101Arg Likely pathogenic ★★ same condition
- AMH p.Pro151Ser Pathogenic ★★ ⚠ same condition
- AMH p.Pro398Leu Uncertain significance ★★ ⚠ same condition
- AMH p.Thr268Ala Uncertain significance ★★ ⚠ same condition
- AMH p.Thr99Ser 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/amh-p-val477ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown