AMHR2 p.Ala219=
c.657C>T · rs138904291 · VCV2889355
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -5.1 |
| Overall | ||
| CADD | 8.343 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0333%
Admixed American · 20/59,986 alleles
Filtering AF
0.0221%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0184%
Overall
0.00452%
73/1,614,046 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0333% | 2,999 |
| Middle Eastern | 0.0164% | 6,082 |
| East Asian | 0.00668% | 14,965 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00364% | 27,443 |
| South Asian | 0.0022% | 45,544 |
| African / African-American | 0.00133% | 74,916 |
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
- AMHR2
- Protein
- p.Ala219=
- Coding
- c.657C>T
- MANE Select
- NM_020547
- dbSNP
- rs138904291
- Type
- single nucleotide variant
- Location
- chr12:53425724 (GRCh38)
- Gene constraint
- LOEUF 0.784 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.34 · 1 PDB
- Residue 219
- the protein kinase domain
Similar variants
- AMHR2 p.Ala168Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- AMHR2 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same type
- AMHR2 p.Arg22Ter Pathogenic/Likely pathogenic ★★ same type
- AMHR2 p.Arg463Cys Pathogenic/Likely pathogenic ★★ same type
- AMHR2 p.Arg471His Pathogenic/Likely pathogenic ★★ ⚠ same type
- AMHR2 p.Ala118Thr Uncertain significance ★★ ⚠ same type
- AMHR2 p.Ala139Val Uncertain significance ★★ ⚠ same type
- AMHR2 p.Arg22Gln Uncertain significance ★★ ⚠ same type
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/amhr2-p-ala219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown