Is COQ8A p.Ala412= (c.1236C>T) pathogenic?

COQ8A p.Ala412= (c.1236C>T) is classified Conflicting classifications of pathogenicity in COQ8A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-11-03). Very rare (popmax 0.00892%, eas); Associated with autosomal recessive ataxia due to ubiquinone deficiency.

What condition is associated with COQ8A p.Ala412= (c.1236C>T)?

COQ8A p.Ala412= (c.1236C>T) is associated with autosomal recessive ataxia due to ubiquinone deficiency (ClinVar).

How common is COQ8A p.Ala412= (c.1236C>T) in the general population?

COQ8A p.Ala412= (c.1236C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

COQ8A p.Ala412=

Q: How is Autosomal recessive ataxia due to ubiquinone deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1236C>T · rs764541059 · VCV873711

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

autosomal recessive ataxia due to ubiquinone deficiency

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 -20	GERP -5
Overall
CADD	0.348	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,858 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00149% 24/1,610,850 alleles · very rare exomes 19/1,458,738 · genomes 5/152,112 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,214
African / African-American	0.00534%	18,715
European (non-Finnish)	0.00127%	78,661
South Asian	0.0011%	90,988

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: COQ8A
Protein: p.Ala412=
Coding: c.1236C>T
MANE Select: NM_020247
dbSNP: rs764541059
Type: single nucleotide variant
Location: chr1:226983834 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.65 · 4 PDB
Residue 412: the protein kinase domain; an α-helix

Full COQ8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive ataxia due to ubiquinone deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive ataxia due to ubiquinone deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

COQ8A c.588+1G>C Likely pathogenic ★★ same condition
COQ8A c.589-3C>G Pathogenic ★★ same condition
COQ8A p.Ala304Val Pathogenic/Likely pathogenic ★★ same condition
COQ8A p.Ala338Val Likely pathogenic ★★ same condition
COQ8A p.Ala339Thr Pathogenic/Likely pathogenic ★★ same condition
COQ8A p.Arg160Ter Pathogenic/Likely pathogenic ★★ same condition
COQ8A p.Arg213Gln Likely pathogenic ★★ same condition
COQ8A p.Arg213Trp Pathogenic/Likely pathogenic ★★ same condition

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/coq8a-p-ala412 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown