COX6A1 p.Ala46=
c.138G>A · VCV3617791
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.133 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.13 | GERP -3.1, phastCons 0.82 |
| Overall | ||
| CADD | 9.781 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,180,048 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00031%
5/1,614,068 alleles · very rare
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
- COX6A1
- Protein
- p.Ala46=
- Coding
- c.138G>A
- MANE Select
- NM_004373
- Type
- single nucleotide variant
- Location
- chr12:120438413 (GRCh38)
- Gene constraint
- LOEUF 1.355 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.06 · 3 PDB
Similar variants
- COX6A1 c.103+1G>C Uncertain significance ★★ same type
- COX6A1 p.Ala2Ser Uncertain significance ★★ ⚠ same type
- COX6A1 p.Arg11Pro Uncertain significance ★★ ⚠ same type
- COX6A1 p.Arg17His Uncertain significance ★★ ⚠ same type
- COX6A1 p.Arg36Cys Uncertain significance ★★ ⚠ same type
- COX6A1 p.Glu107Lys Uncertain significance ★★ ⚠ same type
- COX6A1 p.His62Tyr Uncertain significance ★★ ⚠ same type
- COX6A1 p.His98Tyr 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/cox6a1-p-ala46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown