COX15 p.Pro248=
c.744G>T · rs75208218 · VCV1902336
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00754%, 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 -0.63 | GERP -1.8 |
| Overall | ||
| CADD | 0.924 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00754%
European (non-Finnish) · 89/1,179,954 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00579%
Overall
0.00564%
91/1,613,504 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00754% | 13,258 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,229 |
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
- COX15
- Protein
- p.Pro248=
- Coding
- c.744G>T
- MANE Select
- NM_078470
- dbSNP
- rs75208218
- Type
- single nucleotide variant
- Location
- chr10:99723962 (GRCh38)
- Gene constraint
- LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.29
Similar variants
- COX15 p.Pro248Ala Uncertain significance ★ ⚠ same residue
- COX15 p.Pro248Leu Uncertain significance ★ ⚠ same residue
- COX15 c.272+2T>G Pathogenic/Likely pathogenic ★★ same type
- COX15 c.750+1G>A Likely pathogenic ★★ same type
- COX15 c.750+1G>T Likely pathogenic ★★ same type
- COX15 p.Arg153Ter Pathogenic/Likely pathogenic ★★ same type
- COX15 p.Arg217Trp Pathogenic ★★ same type
- COX15 p.Ser151Ter Pathogenic/Likely pathogenic ★★ 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/cox15-p-pro248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown