CPA5 p.Pro409=
c.1227G>A · rs781949565 · VCV3076530
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.048 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -9.1 | GERP -5 |
| Overall | ||
| CADD | 4.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,996 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00167%
27/1,613,924 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,998 |
| South Asian | 0.0022% | 45,532 |
| European (non-Finnish) | 0.00195% | 51,305 |
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
- CPA5
- Protein
- p.Pro409=
- Coding
- c.1227G>A
- MANE Select
- NM_080385
- dbSNP
- rs781949565
- Type
- single nucleotide variant
- Location
- chr7:130368513 (GRCh38)
- Gene constraint
- LOEUF 1.11 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.56
- Residue 409
- the peptidase m14 domain
Similar variants
- CPA5 p.Ala120Thr Uncertain significance ★ ⚠ same type
- CPA5 p.Ala188Val Uncertain significance ★ ⚠ same type
- CPA5 p.Ala229Val Uncertain significance ★ ⚠ same type
- CPA5 p.Ala350Asp Uncertain significance ★ ⚠ same type
- CPA5 p.Ala356Val Uncertain significance ★ ⚠ same type
- CPA5 p.Ala393Asp Uncertain significance ★ ⚠ same type
- CPA5 p.Ala393Thr Uncertain significance ★ ⚠ same type
- CPA5 p.Ala423Val 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/cpa5-p-pro409 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown