COPA c.228+35A>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 86.8%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +35 | near-intronic (+35 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -4.8 |
| Overall | ||
| CADD | 4.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
86.8%
African / African-American · 64,470/74,248 alleles
Filtering AF
86.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 86%
Overall
57.7%
913,436/1,582,816 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 86.8% | 1 |
| South Asian | 69.7% | 1 |
| Middle Eastern | 63.5% | 2 |
| Amishnot grpmax-eligible | 59.6% | 2 |
| Remaining individualsnot grpmax-eligible | 58.2% | 2 |
| Admixed American | 56.8% | 2 |
| European (non-Finnish) | 55.8% | 2 |
| Finnishnot grpmax-eligible | 52.1% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 50.6% | 2 |
| East Asian | 46.4% | 2 |
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
- COPA
- Coding
- c.228+35A>C
- MANE Select
- NM_004371
- dbSNP
- rs1886419
- Type
- single nucleotide variant
- Location
- chr1:160339874 (GRCh38)
- Gene constraint
- LOEUF 0.098 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.85 · 3 PDB
Similar variants
- COPA p.Arg233His Pathogenic/Likely pathogenic ★★ same type
- COPA p.Glu241Lys Pathogenic ★★ same type
- COPA p.Ala111Thr Uncertain significance ★★ ⚠ same type
- COPA p.Ala176Val Uncertain significance ★★ ⚠ same type
- COPA p.Ala407Val Uncertain significance ★★ ⚠ same type
- COPA p.Ala422Thr Uncertain significance ★★ ⚠ same type
- COPA p.Ala469Val Uncertain significance ★★ ⚠ same type
- COPA p.Ala510Thr Uncertain significance ★★ ⚠ 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/copa-c-228-plus-35a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown