COPB2 p.Pro860del
c.2578_2580del · VCV4084912
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.101%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP 1.3, phastCons 0.99 |
| Overall | ||
| CADD | 17.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.101%
African / African-American · 76/74,932 alleles
Filtering AF
0.083%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0763%
Overall
0.00539%
87/1,613,930 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.101% | 986 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| Admixed American | 0.005% | 19,998 |
| South Asian | 0.0022% | 45,536 |
| European (non-Finnish) | 8.47e-05% | 1,179,976 |
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
- COPB2
- Protein
- p.Pro860del
- Coding
- c.2578_2580del
- MANE Select
- NM_004766
- Type
- Deletion
- Location
- chr3:139358245 (GRCh38)
- Gene constraint
- LOEUF 0.177 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.75 · 2 PDB
- Residue 860
- the 'disordered' region
Similar variants
- COPB2 p.Lys413fs Uncertain significance ★ same type
- COPB2 p.Val222fs Conflicting classifications of pathogenicity ★ same type
- COPB2 c.1206-13_1206-3del Likely benign ★ same type
- COPB2 c.1295-6del Likely benign ★ same type
- COPB2 c.2485-30_2485-21del Likely benign ★ same type
- COPB2 c.229-10_229-9del Likely benign 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/copb2-p-pro860del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown