COX8C p.Ala60=
c.180A>G · VCV4533484
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0968%, 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 -9.3 | GERP -3.9 |
| Overall | ||
| CADD | 0.024 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0968%
European (non-Finnish) · 1,141/1,178,690 alleles
Filtering AF
0.0921%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0902%
Overall
0.0779%
1,257/1,612,716 alleles · ultra-rare
exomes 1,160/1,460,394 · genomes 97/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0968% | 1,033 |
| Admixed American | 0.0683% | 1,464 |
| East Asian | 0.0579% | 1,726 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,837 |
| African / African-American | 0.0133% | 7,503 |
| Finnishnot grpmax-eligible | 0.00469% | 21,343 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,594 |
| South Asian | 0.0011% | 91,056 |
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
- COX8C
- Protein
- p.Ala60=
- Coding
- c.180A>G
- MANE Select
- NM_182971
- Type
- single nucleotide variant
- Location
- chr14:93348081 (GRCh38)
- Gene constraint
- LOEUF 1.876 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 78.94
Similar variants
- COX8C c.127-2A>G Uncertain significance ★ same type
- COX8C p.Ala10Ser Uncertain significance ★ ⚠ same type
- COX8C p.Arg11Cys Uncertain significance ★ ⚠ same type
- COX8C p.Arg12Ser Uncertain significance ★ ⚠ same type
- COX8C p.Arg15Cys Uncertain significance ★ ⚠ same type
- COX8C p.Arg15Ser Uncertain significance ★ ⚠ same type
- COX8C p.Arg16Cys Uncertain significance ★ ⚠ same type
- COX8C p.Arg16His 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/cox8c-p-ala60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown