Is COQ4 p.Pro64= (c.192C>A) pathogenic?

COQ4 p.Pro64= (c.192C>A) is classified Likely benign in COQ4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-02). Very rare (popmax 0.00323%, nfe); Associated with neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome.

How common is COQ4 p.Pro64= (c.192C>A) in the general population?

COQ4 p.Pro64= (c.192C>A) is very rare (popmax 0.00323%, nfe) (gnomAD).

COQ4 p.Pro64=

Q: What condition is associated with COQ4 p.Pro64= (c.192C>A)?

COQ4 p.Pro64= (c.192C>A) 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.192C>A · rs753646987 · VCV2047184

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00323%, 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 -2.1	GERP -3.5
Overall
CADD	1.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00323% European (non-Finnish) · 38/1,176,308 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00312% 50/1,601,868 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0341%	2,937
European (non-Finnish)grpmax	0.00323%	30,955
Remaining individualsnot grpmax-eligible	0.00323%	30,956

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: COQ4
Protein: p.Pro64=
Coding: c.192C>A
MANE Select: NM_016035
dbSNP: rs753646987
Type: single nucleotide variant
Location: chr9:128323137 (GRCh38)
Gene constraint: LOEUF 1.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.56
Residue 64: a UniProt-annotated variant site (in coq10d7)

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.Pro64Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro64 (accessed [today's date]).

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