COQ2 p.Pro46=
c.138C>T · VCV3700589
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00247%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -3 |
| Overall | ||
| CADD | 0.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00247%
South Asian · 2/80,874 alleles
Filtering AF
0.000993%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000819%
Overall
0.00139%
21/1,514,930 alleles · very rare
exomes 21/1,362,808 · genomes 0/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00247% | 40,437 |
| Remaining individualsnot grpmax-eligible | 0.00171% | 58,540 |
| European (non-Finnish) | 0.00159% | 62,958 |
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
- COQ2
- Protein
- p.Pro46=
- Coding
- c.138C>T
- MANE Select
- NM_001358921
- Type
- single nucleotide variant
- Location
- chr4:83284627 (GRCh38)
- Gene constraint
- LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.64
Similar variants
- COQ2 p.Pro46Leu Likely benign ★★ same residue
- COQ2 p.Pro46Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- COQ2 p.Arg123Cys Likely pathogenic ★★ same type
- COQ2 p.Arg147His Pathogenic/Likely pathogenic ★★ same type
- COQ2 p.Gln44Ter Likely pathogenic ★★ same type
- COQ2 p.Ser96Asn Pathogenic ★★ same type
- COQ2 p.Trp24Ter Likely pathogenic ★★ same type
- COQ2 p.Trp87Ter 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/coq2-p-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown