Is COQ8A p.Asp396= (c.1188C>T) pathogenic?

COQ8A p.Asp396= (c.1188C>T) is classified Conflicting classifications of pathogenicity in COQ8A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-12-25). Rare (popmax 0.721%, mid); Associated with autosomal recessive ataxia due to ubiquinone deficiency.

What condition is associated with COQ8A p.Asp396= (c.1188C>T)?

COQ8A p.Asp396= (c.1188C>T) is associated with autosomal recessive ataxia due to ubiquinone deficiency (ClinVar).

How common is COQ8A p.Asp396= (c.1188C>T) in the general population?

COQ8A p.Asp396= (c.1188C>T) is rare (popmax 0.721%, mid) (gnomAD).

COQ8A p.Asp396=

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.1188C>T · rs139133094 · VCV296018

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.721%, mid)

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 -9.3	GERP -4.9
Overall
CADD	6.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.721% Middle Eastern · 43/5,968 alleles

Filtering AF 0.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.49%

Overall 0.0273% 441/1,613,030 alleles · rare exomes 401/1,460,698 · genomes 40/152,332 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.721%	139
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Finnishnot grpmax-eligible	0.0555%	1,801
Admixed American	0.0516%	1,936
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,691
South Asian	0.0296%	3,373
European (non-Finnish)	0.021%	4,758
African / African-American	0.0107%	9,383
East Asian	0.00223%	44,866

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.Asp396=
Coding: c.1188C>T
MANE Select: NM_020247
dbSNP: rs139133094
Type: single nucleotide variant
Location: chr1:226983786 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.65 · 4 PDB
Residue 396: 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-asp396 (accessed [today's date]).

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