CPB2 p.Pro221=
c.663A>G · rs7337140 · VCV3060410
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 87.8%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
CPB2-related disorder
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 -13 | GERP -5.5 |
| Overall | ||
| CADD | 0.025 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
87.8%
African / African-American · 65,296/74,336 alleles
Filtering AF
87.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 87%
Overall
75%
1,187,746/1,583,384 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 87.8% | 1 |
| East Asian | 84.3% | 1 |
| Finnishnot grpmax-eligible | 81.4% | 1 |
| Admixed American | 80.3% | 1 |
| Remaining individualsnot grpmax-eligible | 74.3% | 1 |
| European (non-Finnish) | 73.7% | 1 |
| South Asian | 71% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 70.2% | 1 |
| Middle Eastern | 68.4% | 1 |
| Amishnot grpmax-eligible | 66.3% | 2 |
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
- CPB2
- Protein
- p.Pro221=
- Coding
- c.663A>G
- MANE Select
- NM_001872
- dbSNP
- rs7337140
- Type
- single nucleotide variant
- Location
- chr13:46067346 (GRCh38)
- Gene constraint
- LOEUF 1.373 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.32 · 10 PDB
- Residue 221
- the peptidase m14 domain; a β-strand
Disease context
CPB2-related disorder
Similar variants
- CPB2 p.Ala169Thr Benign same condition
- CPB2 p.Asp226= Benign same condition
- CPB2 p.Asp97= Benign same condition
- CPB2 p.Cys405= Likely benign same condition
- CPB2 p.Glu184= Likely benign same condition
- CPB2 p.Ile251= Benign same condition
- CPB2 p.Ile347Thr Benign ⚠ same condition
- CPB2 p.Gly203_Ile204insTer Uncertain significance same condition
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/cpb2-p-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown