AMHR2 p.Ser346=
c.1038G>A · rs784890 · VCV1221414
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 48%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -5.3 |
| Overall | ||
| CADD | 2.413 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
48%
African / African-American · 35,856/74,650 alleles
Filtering AF
47.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 47.4%
Overall
2.64%
42,643/1,613,314 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 48% | 2 |
| Middle Eastern | 3.73% | 27 |
| Admixed American | 3.69% | 27 |
| Remaining individualsnot grpmax-eligible | 3.5% | 29 |
| Ashkenazi Jewishnot grpmax-eligible | 0.426% | 235 |
| European (non-Finnish) | 0.162% | 617 |
| South Asian | 0.115% | 867 |
| Finnishnot grpmax-eligible | 0.0251% | 3,992 |
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.Ser346=
- Coding
- c.1038G>A
- MANE Select
- NM_020547
- dbSNP
- rs784890
- Type
- single nucleotide variant
- Location
- chr12:53429523 (GRCh38)
- Gene constraint
- LOEUF 0.784 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.34 · 1 PDB
- Residue 346
- 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-ser346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown