COPB2 p.Gly531=
c.1593C>T · VCV4521924
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.61 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.62 | gain · loss 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.41 | GERP -1.6, phastCons 0.97 |
| Overall | ||
| CADD | 19.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,954 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000205%
3/1,461,608 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,954 |
| European (non-Finnish) | 0.00017% | 589,908 |
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.Gly531=
- Coding
- c.1593C>T
- MANE Select
- NM_004766
- Type
- single nucleotide variant
- Location
- chr3:139367098 (GRCh38)
- Gene constraint
- LOEUF 0.177 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.75 · 2 PDB
Similar variants
- COPB2 p.Glu646Lys Uncertain significance ★★ ⚠ same type
- COPB2 p.Glu879Lys Uncertain significance ★★ ⚠ same type
- COPB2 p.Ile864Thr Uncertain significance ★★ ⚠ same type
- COPB2 p.Leu649Phe Uncertain significance ★★ ⚠ same type
- COPB2 p.Ser135Ala Uncertain significance ★★ ⚠ same type
- COPB2 c.1095-23T>C Benign ★★ same type
- COPB2 c.1401+12C>T Likely benign ★★ same type
- COPB2 c.141+20G>T 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-gly531 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown