Is COQ9 p.Pro80= (c.240C>G) pathogenic?

COQ9 p.Pro80= (c.240C>G) is classified Benign/Likely benign in COQ9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-11). Low-frequency (popmax 1.38%, eas); Associated with encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome.

How common is COQ9 p.Pro80= (c.240C>G) in the general population?

COQ9 p.Pro80= (c.240C>G) is low-frequency (popmax 1.38%, eas) (gnomAD).

COQ9 p.Pro80=

Q: What condition is associated with COQ9 p.Pro80= (c.240C>G)?

COQ9 p.Pro80= (c.240C>G) is associated with encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (ClinVar).

Q: How is Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome inherited?

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

c.240C>G · rs2301773 · VCV320005

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, eas)

Conditions

encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.39	GERP 0.61, phastCons 0.99
Overall
CADD	11.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.38% East Asian · 619/44,892 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0388% 626/1,614,226 alleles · low-frequency exomes 605/1,461,876 · genomes 21/152,350 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.38%	73
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.0011%	91,080
European (non-Finnish)	0.000169%	590,012

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: COQ9
Protein: p.Pro80=
Coding: c.240C>G
MANE Select: NM_020312
dbSNP: rs2301773
Type: single nucleotide variant
Location: chr16:57451206 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.16 · 5 PDB
Residue 80: the 'disordered' region

Full COQ9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

COQ9 p.Pro80Ala Uncertain significance ★★ ⚠ same residue
COQ9 c.522-1G>A Likely pathogenic ★★ same condition
COQ9 c.711+3G>C Pathogenic ★★ same condition
COQ9 p.Arg244Ter Pathogenic/Likely pathogenic ★★ same condition
COQ9 p.Arg102His Uncertain significance ★★ ⚠ same condition
COQ9 p.Arg156Trp Uncertain significance ★★ ⚠ same condition
COQ9 p.Ser7Phe Uncertain significance ★★ ⚠ same condition
COQ9 c.379-16G>C Benign/Likely benign ★★ 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/coq9-p-pro80 (accessed [today's date]).

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