AMER1 p.Leu896=
c.2688C>T · rs769040672 · VCV1992171
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0192%, afr)
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 -0.72 | GERP -1 |
| Overall | ||
| CADD | 0.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0192%
African / African-American · 11/57,303 alleles
Filtering AF
0.0108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00829%
Overall
0.00207%
25/1,210,519 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0192% | 5,209 |
| South Asian | 0.0106% | 9,468 |
| Admixed American | 0.00436% | 22,935 |
| East Asian | 0.00296% | 33,760 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,615 |
| European (non-Finnish) | 0.000447% | 223,828 |
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.Leu896=
- Coding
- c.2688C>T
- MANE Select
- NM_152424
- dbSNP
- rs769040672
- Type
- single nucleotide variant
- Location
- chrX:64190599 (GRCh38)
- Structure
- AlphaFold pLDDT 48.88 · 3 PDB
Similar variants
- 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
- AMER1 p.Ala202Gly Uncertain significance ★★ ⚠ same type
- AMER1 p.Ala229Pro 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/amer1-p-leu896 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown