CPOX p.Leu157=
c.469C>T · rs148466102 · VCV764617
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00517%, 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 -2.4, phastCons 1 |
| Overall | ||
| CADD | 8.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00517%
European (non-Finnish) · 61/1,179,970 alleles
Filtering AF
0.0041%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00372%
Overall
0.00397%
64/1,613,828 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00517% | 19,344 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,232 |
| South Asian | 0.0011% | 91,052 |
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.Leu157=
- Coding
- c.469C>T
- MANE Select
- NM_000097
- dbSNP
- rs148466102
- Type
- single nucleotide variant
- Location
- chr3:98593036 (GRCh38)
- Gene constraint
- LOEUF 0.8 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 1 PDB
- Residue 157
- a UniProt-annotated variant site (in hcp); an α-helix
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-leu157 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown