COPB2 p.Ala719=
c.2157G>A · VCV3607270
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0626%, sas)
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 -20 | GERP -4.5 |
| Overall | ||
| CADD | 0.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0626%
South Asian · 57/91,088 alleles
Filtering AF
0.0496%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0449%
Overall
0.00434%
70/1,614,200 alleles · ultra-rare
exomes 65/1,461,892 · genomes 5/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0626% | 1,598 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.00267% | 37,522 |
| European (non-Finnish) | 0.000847% | 118,004 |
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.Ala719=
- Coding
- c.2157G>A
- MANE Select
- NM_004766
- Type
- single nucleotide variant
- Location
- chr3:139361134 (GRCh38)
- Gene constraint
- LOEUF 0.177 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.75 · 2 PDB
Similar variants
- COPB2 p.Ala719Thr Uncertain significance ★ ⚠ same residue
- COPB2 p.Ala719Val Uncertain significance ★ ⚠ same residue
- 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
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-ala719 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown