COQ9 p.Pro34=

Q: Is COQ9 p.Pro34= (c.102G>A) pathogenic?

COQ9 p.Pro34= (c.102G>A) is classified Benign in COQ9 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 5.26%, mid) — too common for a highly-penetrant pathogenic allele; Associated with encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome.

Q: What condition is associated with COQ9 p.Pro34= (c.102G>A)?

COQ9 p.Pro34= (c.102G>A) is associated with encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (ClinVar).

Q: How common is COQ9 p.Pro34= (c.102G>A) in the general population?

COQ9 p.Pro34= (c.102G>A) is common (popmax 5.26%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.102G>A · rs223864 · VCV136993

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.26%, mid) — too common for a highly-penetrant pathogenic allele

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.5
Overall
CADD	2.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.26% Middle Eastern · 317/6,032 alleles

Filtering AF 4.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.59%

Overall 2.97% 47,870/1,613,974 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.26%	19
European (non-Finnish)	3.32%	30
Remaining individualsnot grpmax-eligible	3.01%	33
Ashkenazi Jewishnot grpmax-eligible	2.99%	33
African / African-American	2.66%	38
Admixed American	1.88%	53
Finnishnot grpmax-eligible	1.83%	55
South Asian	1.36%	74
Amishnot grpmax-eligible	0.987%	101
East Asian	0.0847%	1,181

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.Pro34=
Coding: c.102G>A
MANE Select: NM_020312
dbSNP: rs223864
Type: single nucleotide variant
Location: chr16:57451068 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.16 · 5 PDB

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.Pro34Leu 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-pro34 (accessed [today's date]).

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