Is COQ4 p.Arg80= (c.240C>T) pathogenic?

COQ4 p.Arg80= (c.240C>T) is classified Likely benign in COQ4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Very rare (popmax 0.00636%, nfe); Associated with neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome.

How common is COQ4 p.Arg80= (c.240C>T) in the general population?

COQ4 p.Arg80= (c.240C>T) is very rare (popmax 0.00636%, nfe) (gnomAD).

COQ4 p.Arg80=

Q: What condition is associated with COQ4 p.Arg80= (c.240C>T)?

COQ4 p.Arg80= (c.240C>T) is associated with neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (ClinVar).

Q: How is Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome inherited?

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

c.240C>T · rs751428679 · VCV2153424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Conditions

neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome

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 -2.3	GERP -3.5
Overall
CADD	1.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00636% European (non-Finnish) · 75/1,179,998 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00508% 82/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,733
South Asian	0.00439%	22,771
Remaining individualsnot grpmax-eligible	0.0032%	31,240
East Asian	0.00223%	44,900

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: COQ4
Protein: p.Arg80=
Coding: c.240C>T
MANE Select: NM_016035
dbSNP: rs751428679
Type: single nucleotide variant
Location: chr9:128325180 (GRCh38)
Gene constraint: LOEUF 1.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.56

Full COQ4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

COQ4 p.Arg80Cys Uncertain significance ★★ ⚠ same residue
COQ4 c.300-2A>G Likely pathogenic ★★ same condition
COQ4 c.402+1G>A Pathogenic/Likely pathogenic ★★ same condition
COQ4 c.402+1G>C Pathogenic/Likely pathogenic ★★ same condition
COQ4 p.Ala71Thr Likely pathogenic ★★ same condition
COQ4 p.Arg141Ter Pathogenic/Likely pathogenic ★★ same condition
COQ4 p.Arg205Ter Pathogenic/Likely pathogenic ★★ same condition
COQ4 p.Arg240Cys 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/coq4-p-arg80 (accessed [today's date]).

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