Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 8.39%, 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 | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.73 | GERP 1.6, phastCons 0.25 |
| Overall | ||
| CADD | 13.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.39%
African / African-American · 6,291/74,996 alleles
Filtering AF
8.22%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.14%
Overall
0.643%
10,354/1,609,600 alleles · common
exomes 6,316/1,457,228 · genomes 4,038/152,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.39% | 12 |
| East Asian | 4.63% | 22 |
| Remaining individualsnot grpmax-eligible | 1.09% | 91 |
| Admixed American | 0.819% | 122 |
| Middle Eastern | 0.479% | 209 |
| South Asian | 0.375% | 267 |
| Ashkenazi Jewishnot grpmax-eligible | 0.326% | 307 |
| European (non-Finnish) | 0.0307% | 3,254 |
| Finnishnot grpmax-eligible | 0.00315% | 31,763 |
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
- COX8A
- Protein
- p.Leu8=
- Coding
- c.22C>T
- MANE Select
- NM_004074
- dbSNP
- rs7130187
- Type
- single nucleotide variant
- Location
- chr11:63974702 (GRCh38)
- Gene constraint
- LOEUF 1.922 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.74 · 4 PDB
Similar variants
- COX8A p.Trp57Cys Uncertain significance ★★ ⚠ same type
- COX8A c.114+17G>A Likely benign ★★ same type
- COX8A p.Arg23Cys Benign/Likely benign ★★ same type
- COX8A p.Ile37= Benign/Likely benign ★★ same type
- COX8A p.Ile58= Benign/Likely benign ★★ same type
- COX8A p.Pro31= Likely benign ★★ same type
- COX8A p.Glu39Gly Uncertain significance ★ ⚠ same type
- COX8A p.Glu39Lys 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/cox8a-p-leu8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown