COA8 p.Asp141=
c.423C>T · rs745349308 · VCV2882963
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0401%, 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 -0.17 | GERP -2.8, phastCons 0.42 |
| Overall | ||
| CADD | 1.587 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0401%
Admixed American · 24/59,898 alleles
Filtering AF
0.0276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0235%
Overall
0.00155%
25/1,613,296 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0401% | 2,496 |
| European (non-Finnish) | 8.48e-05% | 1,179,660 |
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
- COA8
- Protein
- p.Asp141=
- Coding
- c.423C>T
- MANE Select
- NM_001370595
- dbSNP
- rs745349308
- Type
- single nucleotide variant
- Location
- chr14:103587311 (GRCh38)
- Gene constraint
- LOEUF 1.305 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.19
- Residue 141
- a UniProt-annotated variant site (in mc4dn17; low steady-state levels of cox subunits and reduced levels of fully assembled cox; highly decreased cox complex iv activity and decreased cox complex ii activity in muscle)
Similar variants
- COA8 p.Arg66Ter Pathogenic ★★ same type
- COA8 c.-32C>G Uncertain significance ★★ ⚠ same type
- COA8 p.Ala140Val Uncertain significance ★★ ⚠ same type
- COA8 p.Ala176Gly Uncertain significance ★★ ⚠ same type
- COA8 p.Ala27Val Uncertain significance ★★ ⚠ same type
- COA8 p.Arg164Cys Uncertain significance ★★ ⚠ same type
- COA8 p.Arg17Leu Uncertain significance ★★ ⚠ same type
- COA8 p.Arg34Leu 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/coa8-p-asp141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown