COPB2 p.Ala497=
c.1491T>C · rs371807575 · VCV2065999
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0311%, 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 3 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 10.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0311%
European (non-Finnish) · 367/1,179,910 alleles
Filtering AF
0.0285%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0274%
Overall
0.0236%
381/1,613,846 alleles · ultra-rare
exomes 363/1,461,620 · genomes 18/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0311% | 3,215 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| Admixed American | 0.005% | 19,991 |
| African / African-American | 0.00133% | 74,924 |
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.Ala497=
- Coding
- c.1491T>C
- MANE Select
- NM_004766
- dbSNP
- rs371807575
- Type
- single nucleotide variant
- Location
- chr3:139368199 (GRCh38)
- Gene constraint
- LOEUF 0.177 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.75 · 2 PDB
- Residue 497
- an α-helix
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-ala497 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown