COX5A p.Ala12=
c.36C>T · rs369373998 · VCV2645552
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.715%, mid)
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 -0.47 | GERP -4.4, phastCons 0.038 |
| Overall | ||
| CADD | 5.677 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.715%
Middle Eastern · 24/3,356 alleles
Filtering AF
0.493%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.42%
Overall
0.327%
4,028/1,232,822 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.715% | 140 |
| European (non-Finnish) | 0.378% | 264 |
| Ashkenazi Jewishnot grpmax-eligible | 0.31% | 323 |
| Remaining individualsnot grpmax-eligible | 0.267% | 375 |
| Admixed American | 0.152% | 657 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| African / African-American | 0.0574% | 1,742 |
| Finnishnot grpmax-eligible | 0.0275% | 3,635 |
| South Asian | 0.0164% | 6,097 |
| East Asian | 0.00315% | 31,696 |
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
- COX5A
- Protein
- p.Ala12=
- Coding
- c.36C>T
- MANE Select
- NM_004255
- dbSNP
- rs369373998
- Type
- single nucleotide variant
- Location
- chr15:74937979 (GRCh38)
- Gene constraint
- LOEUF 0.82 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 88.21 · 3 PDB
Similar variants
- COX5A p.Ser25Cys Likely benign ★★ same type
- COX5A p.Ala13Thr Uncertain significance ★ ⚠ same type
- COX5A p.Ala32Asp Uncertain significance ★ ⚠ same type
- COX5A p.Ala32Thr Uncertain significance ★ ⚠ same type
- COX5A p.Ala54Gly Uncertain significance ★ ⚠ same type
- COX5A p.Arg107Ser Uncertain significance ★ ⚠ same type
- COX5A p.Arg55Cys Uncertain significance ★ ⚠ same type
- COX5A p.Arg94Gln 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/cox5a-p-ala12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown