COX6A1 p.Ala2=
c.6G>A · rs1462906657 · VCV752197
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 1.3 | GERP -0.46, phastCons 0.004 |
| Overall | ||
| CADD | 9.404 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,946 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000186%
3/1,613,260 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,973 |
| European (non-Finnish) | 8.48e-05% | 1,179,883 |
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.Ala2=
- Coding
- c.6G>A
- MANE Select
- NM_004373
- dbSNP
- rs1462906657
- Type
- single nucleotide variant
- Location
- chr12:120438132 (GRCh38)
- Gene constraint
- LOEUF 1.355 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.06 · 3 PDB
Similar variants
- COX6A1 p.Ala2Ser Uncertain significance ★★ ⚠ same residue
- COX6A1 p.Ala2Val Uncertain significance ★ ⚠ same residue
- COX6A1 c.103+1G>C 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
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-ala2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown