CPAP p.Pro457=
c.1371G>A · rs770254231 · VCV210656
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
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 -3.1 | GERP -2.9 |
| Overall | ||
| CADD | 0.676 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/60,012 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00785%
Overall
0.00248%
40/1,614,128 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,456 |
| African / African-American | 0.00667% | 14,987 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00169% | 59,002 |
| Finnishnot grpmax-eligible | 0.00156% | 64,044 |
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
- CPAP
- Protein
- p.Pro457=
- Coding
- c.1371G>A
- MANE Select
- NM_018451
- dbSNP
- rs770254231
- Type
- single nucleotide variant
- Location
- chr13:24906667 (GRCh38)
- Structure
- AlphaFold pLDDT 56.70 · 6 PDB
- Residue 457
- the 'disordered' region
Similar variants
- CPAP p.Pro457Leu Uncertain significance ★★ ⚠ same residue
- CPAP c.2693-2A>G Likely pathogenic ★★ same type
- CPAP p.Arg1298Gln Likely pathogenic ★★ same type
- CPAP p.Arg378Ter Pathogenic ★★ same type
- CPAP p.Arg566Ter Pathogenic/Likely pathogenic ★★ same type
- CPAP p.Arg902Ter Pathogenic/Likely pathogenic ★★ same type
- CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same type
- CPAP p.Gln14Ter 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/cpap-p-pro457 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown