CPOX p.Val74=
c.222G>A · rs368067440 · VCV732948
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.529%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -0.98 |
| Overall | ||
| CADD | 10.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.529%
African / African-American · 371/70,118 alleles
Filtering AF
0.485%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.467%
Overall
0.0296%
432/1,461,154 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.529% | 189 |
| Middle Eastern | 0.0783% | 1,277 |
| Admixed American | 0.05% | 2,000 |
| Remaining individualsnot grpmax-eligible | 0.0283% | 3,530 |
| East Asian | 0.00246% | 40,622 |
| European (non-Finnish) | 0.00188% | 53,079 |
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.Val74=
- Coding
- c.222G>A
- MANE Select
- NM_000097
- dbSNP
- rs368067440
- Type
- single nucleotide variant
- Location
- chr3:98593283 (GRCh38)
- Gene constraint
- LOEUF 0.8 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 1 PDB
- Residue 74
- a UniProt-annotated variant site (in hcp)
Similar variants
- CPOX p.Val74Leu Uncertain significance ★ ⚠ same residue
- 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
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-val74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown