AMER1 p.Pro538=
c.1614C>T · rs760240495 · VCV1924609
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0435%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.27 | GERP 0.44, phastCons 0.9 |
| Overall | ||
| CADD | 3.591 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0435%
African / African-American · 25/57,411 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0258%
Overall
0.00206%
25/1,210,849 alleles · ultra-rare
exomes 12/1,098,222 · genomes 13/112,627 · joint denominator
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.Pro538=
- Coding
- c.1614C>T
- MANE Select
- NM_152424
- dbSNP
- rs760240495
- Type
- single nucleotide variant
- Location
- chrX:64191673 (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-pro538 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown