CPE p.Asp275=
c.825C>T · rs184912639 · VCV2714897
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, 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 -7.3 | GERP -4.1 |
| Overall | ||
| CADD | 2.774 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
Admixed American · 16/60,002 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00279%
45/1,614,036 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0267% | 3,750 |
| East Asian | 0.0134% | 7,478 |
| South Asian | 0.00769% | 13,012 |
| Finnishnot grpmax-eligible | 0.00469% | 21,338 |
| African / African-American | 0.00267% | 37,517 |
| European (non-Finnish) | 0.000932% | 107,269 |
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
- CPE
- Protein
- p.Asp275=
- Coding
- c.825C>T
- MANE Select
- NM_001873
- dbSNP
- rs184912639
- Type
- single nucleotide variant
- Location
- chr4:165484456 (GRCh38)
- Gene constraint
- LOEUF 0.565 · pLI 0.83 (gnomAD)
- Structure
- AlphaFold pLDDT 90.83
- Residue 275
- a UniProt-annotated variant site (in bdvs); the peptidase m14 domain
Similar variants
- CPE p.Arg121Ter Pathogenic ★★ same type
- CPE p.Arg262Trp Uncertain significance ★★ ⚠ same type
- CPE p.Arg297Trp Uncertain significance ★★ ⚠ same type
- CPE p.Asp251Gly Uncertain significance ★★ ⚠ same type
- CPE p.Asp304Ala Uncertain significance ★★ ⚠ same type
- CPE p.Trp21Cys Uncertain significance ★★ ⚠ same type
- CPE c.307+13C>T Likely benign ★★ same type
- CPE c.672+11C>T Likely benign ★★ 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/cpe-p-asp275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown