COX15 p.Pro252fs
c.755del · VCV3589777
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 9 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP 0.44, phastCons 0.92 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- COX15
- Protein
- p.Pro252fs
- Coding
- c.755del
- MANE Select
- NM_078470
- Type
- Deletion
- Location
- chr10:99721064 (GRCh38)
- Gene constraint
- LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.29
Disease context
cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Fatal infantile cytochrome C oxidase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- COX15 p.Ile347fs Conflicting classifications of pathogenicity ★ same condition
- COX15 p.Pro252= Likely benign ★ same residue
- COX15 c.750+1G>A Likely pathogenic ★★ same condition
- COX15 c.750+1G>T Likely pathogenic ★★ same condition
- COX15 p.Arg153Ter Pathogenic/Likely pathogenic ★★ same condition
- COX15 p.Arg217Trp Pathogenic ★★ same condition
- COX15 p.Ser151Ter Pathogenic/Likely pathogenic ★★ same condition
- COX15 p.Ser229Ter Pathogenic/Likely pathogenic ★★ same condition
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-pro252fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown