Is COQ8A p.Ser439fs (c.1315dup) pathogenic?

COQ8A p.Ser439fs (c.1315dup) is classified Pathogenic/Likely pathogenic in COQ8A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-26). Very rare (popmax 0.00667%, afr); Associated with autosomal recessive ataxia due to ubiquinone deficiency.

What condition is associated with COQ8A p.Ser439fs (c.1315dup)?

COQ8A p.Ser439fs (c.1315dup) is associated with autosomal recessive ataxia due to ubiquinone deficiency (ClinVar).

How common is COQ8A p.Ser439fs (c.1315dup) in the general population?

COQ8A p.Ser439fs (c.1315dup) is very rare (popmax 0.00667%, afr) (gnomAD).

COQ8A p.Ser439fs

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.1315dup · rs781548895 · VCV2875719

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -1.4, phastCons 0.43
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,932 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00031% 5/1,613,760 alleles · very rare exomes 1/1,461,578 · genomes 4/152,182 · joint denominator

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.Ser439fs
Coding: c.1315dup
MANE Select: NM_020247
dbSNP: rs781548895
Type: Duplication
Location: chr1:226984151 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.65 · 4 PDB
Residue 439: the protein kinase domain

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 p.Ser616fs Pathogenic ★★ same condition
COQ8A c.*810_*811insT Benign ★★ same condition
COQ8A c.1573-1dup Likely pathogenic ★ same condition
COQ8A p.Arg527fs Pathogenic ★ same condition
COQ8A p.Ser582fs Pathogenic ★ same condition
COQ8A c.1081-1_1082dup Conflicting classifications of pathogenicity ★ same condition
COQ8A p.Ser439Asn Uncertain significance ★ ⚠ same residue
COQ8A p.Ser439= Likely benign ★ same residue

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-ser439fs (accessed [today's date]).

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