COPB2 p.Ala344=
c.1032A>C · VCV4084032
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0149%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>C here scores Δ0.38 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.13 | GERP -3.2, phastCons 0.75 |
| Overall | ||
| CADD | 6.411 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0149%
European (non-Finnish) · 176/1,180,016 alleles
Filtering AF
0.0131%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.0113%
182/1,614,060 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0149% | 6,705 |
| African / African-American | 0.004% | 24,981 |
| Admixed American | 0.00333% | 29,997 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Ala344=
- Coding
- c.1032A>C
- MANE Select
- NM_004766
- Type
- single nucleotide variant
- Location
- chr3:139373275 (GRCh38)
- Gene constraint
- LOEUF 0.177 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.75 · 2 PDB
- Residue 344
- a β-strand
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-ala344 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown