Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 88.7%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
hereditary coproporphyria
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 0.028 | GERP -1.1, phastCons 0.81 |
| Overall | ||
| CADD | 8.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
88.7%
African / African-American · 66,458/74,948 alleles
Filtering AF
88.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 87.9%
Overall
69.3%
1,117,963/1,613,094 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 88.7% | 1 |
| East Asian | 78% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 72.9% | 1 |
| Finnishnot grpmax-eligible | 71.1% | 1 |
| Middle Eastern | 70.9% | 1 |
| Remaining individualsnot grpmax-eligible | 70% | 1 |
| European (non-Finnish) | 67.8% | 1 |
| Admixed American | 67.4% | 1 |
| South Asian | 66.4% | 2 |
| Amishnot grpmax-eligible | 59.6% | 2 |
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.Glu330=
- Coding
- c.990A>G
- MANE Select
- NM_000097
- dbSNP
- rs1729995
- Type
- single nucleotide variant
- Location
- chr3:98585623 (GRCh38)
- Gene constraint
- LOEUF 0.8 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 1 PDB
- Residue 330
- a UniProt-annotated variant site (in hcp); a β-strand
Disease context
hereditary coproporphyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hereditary coproporphyria (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adolescent, Adult
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- CPOX p.Gln160Ter Pathogenic ★★ same condition
- CPOX p.Glu201Lys Pathogenic/Likely pathogenic ★★ same condition
- CPOX p.Lys404Glu Pathogenic/Likely pathogenic ★★ same condition
- CPOX p.Arg60Gly Uncertain significance ★★ ⚠ same condition
- CPOX p.Thr56Met Uncertain significance ★★ ⚠ same condition
- CPOX p.Val16Gly Uncertain significance ★★ ⚠ same condition
- CPOX c.1172+14A>G Benign ★★ same condition
- CPOX c.556+9G>A Benign/Likely benign ★★ 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/cpox-p-glu330 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown