AMER1 p.Asp731=
c.2193C>T · VCV3612705
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0459%, mid)
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 0.16 | GERP -3.7, phastCons 0.78 |
| Overall | ||
| CADD | 2.182 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0459%
Middle Eastern · 2/4,355 alleles
Filtering AF
0.00812%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0034%
Overall
0.000455%
5/1,098,252 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0459% | 2,178 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,659 |
| European (non-Finnish) | 0.000223% | 447,832 |
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
- AMER1
- Protein
- p.Asp731=
- Coding
- c.2193C>T
- MANE Select
- NM_152424
- Type
- single nucleotide variant
- Location
- chrX:64191094 (GRCh38)
- Structure
- AlphaFold pLDDT 48.88 · 3 PDB
Similar variants
- AMER1 p.Asp731Gly Benign ★ same residue
- AMER1 p.Asp731fs Uncertain significance ★ same residue
- AMER1 p.Arg353Ter Pathogenic ★★ same type
- AMER1 p.Arg358Ter Pathogenic ★★ same type
- AMER1 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same type
- AMER1 p.Gln189Ter Pathogenic ★★ same type
- AMER1 p.Gln335Ter Pathogenic ★★ same type
- AMER1 p.Glu191Ter Pathogenic/Likely pathogenic ★★ 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/amer1-p-asp731 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown