Is COQ8A p.Pro602Arg (c.1805C>G) pathogenic?

COQ8A p.Pro602Arg (c.1805C>G) is classified Conflicting classifications of pathogenicity in COQ8A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.9845); Very rare (popmax 0.005%, amr); Associated with autosomal recessive ataxia due to ubiquinone deficiency.

What condition is associated with COQ8A p.Pro602Arg (c.1805C>G)?

COQ8A p.Pro602Arg (c.1805C>G) is associated with autosomal recessive ataxia due to ubiquinone deficiency (ClinVar).

How common is COQ8A p.Pro602Arg (c.1805C>G) in the general population?

COQ8A p.Pro602Arg (c.1805C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about COQ8A p.Pro602Arg (c.1805C>G)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

COQ8A p.Pro602Arg

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.1805C>G · rs61995958 · VCV976102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive ataxia due to ubiquinone deficiency

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic · top 9% in COQ8A
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -15.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 25 kb · p 0.028 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00136% 22/1,613,924 alleles · very rare exomes 19/1,461,872 · genomes 3/152,052 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,701
Admixed Americangrpmax	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0032%	31,238
South Asian	0.0011%	91,082
European (non-Finnish)	0.000678%	147,500

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro602Arg
Coding: c.1805C>G
MANE Select: NM_020247
dbSNP: rs61995958
Type: single nucleotide variant
Location: chr1:226986598 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.65 · 4 PDB
Residue 602: an α-helix; a UniProt-annotated variant site (in coq10d4)

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.Pro602Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
COQ8A p.Pro602Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro602arg (accessed [today's date]).

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