COX18 p.Leu58=
c.174G>A · rs377697467 · VCV512415
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, 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 0.72 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 13.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
European (non-Finnish) · 197/1,171,042 alleles
Filtering AF
0.0149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0141%
Overall
0.0129%
206/1,592,860 alleles · ultra-rare
exomes 199/1,440,586 · genomes 7/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0168% | 5,944 |
| Remaining individualsnot grpmax-eligible | 0.013% | 7,709 |
| African / African-American | 0.00134% | 74,632 |
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
- COX18
- Protein
- p.Leu58=
- Coding
- c.174G>A
- MANE Select
- NM_001297732
- dbSNP
- rs377697467
- Type
- single nucleotide variant
- Location
- chr4:73069476 (GRCh38)
- Gene constraint
- LOEUF 1.682 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.42
Similar variants
- COX18 p.Arg252Cys Uncertain significance ★★ ⚠ same type
- COX18 p.Ala110Val Uncertain significance ★ ⚠ same type
- COX18 p.Ala131Ser Uncertain significance ★ ⚠ same type
- COX18 p.Ala187Pro Uncertain significance ★ ⚠ same type
- COX18 p.Ala187Val Uncertain significance ★ same type
- COX18 p.Ala195Ser Uncertain significance ★ ⚠ same type
- COX18 p.Ala26Val Uncertain significance ★ ⚠ same type
- COX18 p.Ala325Thr 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/cox18-p-leu58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown