CPB2 p.Cys405=
c.1215T>C · rs138269290 · VCV3035536
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.554%, afr)
Conditions
1
CPB2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.012 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.43 | GERP -5.5 |
| Overall | ||
| CADD | 1.924 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.554%
African / African-American · 416/75,060 alleles
Filtering AF
0.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.493%
Overall
0.0285%
460/1,614,210 alleles · rare
exomes 215/1,461,870 · genomes 245/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.554% | 180 |
| Remaining individualsnot grpmax-eligible | 0.0496% | 2,016 |
| Admixed American | 0.0133% | 7,503 |
| South Asian | 0.0011% | 91,088 |
| European (non-Finnish) | 0.000339% | 295,008 |
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.Cys405=
- Coding
- c.1215T>C
- MANE Select
- NM_001872
- dbSNP
- rs138269290
- Type
- single nucleotide variant
- Location
- chr13:46053671 (GRCh38)
- Gene constraint
- LOEUF 1.373 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.32 · 10 PDB
- Residue 405
- the peptidase m14 domain; an α-helix
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.Glu184= Likely benign same condition
- CPB2 p.Ile251= Benign same condition
- CPB2 p.Ile347Thr Benign same condition
- CPB2 p.Pro221= 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-cys405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown