COX10 p.Ser433=
c.1299C>T · rs777894321 · VCV667517
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00883%, 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 -5.3 | GERP -2.4 |
| Overall | ||
| CADD | 0.222 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00883%
European (non-Finnish) · 104/1,177,350 alleles
Filtering AF
0.00742%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00694%
Overall
0.00691%
111/1,605,456 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00883% | 11,321 |
| Admixed American | 0.00668% | 14,965 |
| East Asian | 0.00223% | 44,814 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,288 |
| South Asian | 0.0011% | 90,834 |
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
- COX10
- Protein
- p.Ser433=
- Coding
- c.1299C>T
- MANE Select
- NM_001303
- dbSNP
- rs777894321
- Type
- single nucleotide variant
- Location
- chr17:14207180 (GRCh38)
- Gene constraint
- LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.11
Similar variants
- COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same type
- COX10 p.Gln230Ter Likely pathogenic ★★ same type
- COX10 p.Pro225Leu Likely pathogenic ★★ same type
- COX10 c.-89G>C Uncertain significance ★★ same type
- COX10 c.-89G>T Uncertain significance ★★ same type
- COX10 p.Ala174Thr Uncertain significance ★★ ⚠ same type
- COX10 p.Ala175Ser Uncertain significance ★★ ⚠ same type
- COX10 p.Ala175Val 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/cox10-p-ser433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown