CPOX p.Leu229=
c.685C>T · rs199774737 · VCV2415391
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00373%, nfe)
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 1.8 | GERP -1.2, phastCons 0.97 |
| Overall | ||
| CADD | 7.846 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00373%
European (non-Finnish) · 44/1,180,016 alleles
Filtering AF
0.00283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00252%
Overall
0.00273%
44/1,614,008 alleles · very rare
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
- CPOX
- Protein
- p.Leu229=
- Coding
- c.685C>T
- MANE Select
- NM_000097
- dbSNP
- rs199774737
- Type
- single nucleotide variant
- Location
- chr3:98591027 (GRCh38)
- Gene constraint
- LOEUF 0.8 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 1 PDB
- Residue 229
- a UniProt-annotated variant site (in hcp)
Similar variants
- CPOX p.Cys239Ter Pathogenic ★★ same type
- CPOX p.Gln160Ter Pathogenic ★★ same type
- CPOX p.Glu201Lys Pathogenic/Likely pathogenic ★★ same type
- CPOX p.Lys404Glu Pathogenic/Likely pathogenic ★★ same type
- CPOX c.811+5G>C Uncertain significance ★★ same type
- CPOX p.Ala293Thr Uncertain significance ★★ ⚠ same type
- CPOX p.Ala83Val Uncertain significance ★★ ⚠ same type
- CPOX p.Ala89Val 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/cpox-p-leu229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown