Is COQ2 p.Pro20Ser (c.58C>T) pathogenic?

COQ2 p.Pro20Ser (c.58C>T) is classified Uncertain significance in COQ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Very rare (popmax 0.000261%, nfe); Associated with coenzyme Q10 deficiency, primary, 1.

What condition is associated with COQ2 p.Pro20Ser (c.58C>T)?

COQ2 p.Pro20Ser (c.58C>T) is associated with coenzyme Q10 deficiency, primary, 1 (ClinVar).

How common is COQ2 p.Pro20Ser (c.58C>T) in the general population?

COQ2 p.Pro20Ser (c.58C>T) is very rare (popmax 0.000261%, nfe) (gnomAD).

COQ2 p.Pro20Ser

c.58C>T · rs1314035160 · VCV2440515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000261%, nfe)

Conditions

coenzyme Q10 deficiency, primary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -1.3
Overall
CADD	1.574	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000261% European (non-Finnish) · 3/1,149,812 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000195% 3/1,539,644 alleles · very rare exomes 2/1,387,410 · genomes 1/152,234 · joint denominator

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: COQ2
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_001358921 · reported on NM_015697
dbSNP: rs1314035160
Type: single nucleotide variant
Location: chr4:83284857 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.64

Full COQ2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

coenzyme Q10 deficiency, primary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COQ2 p.Arg123Cys Likely pathogenic ★★ same condition
COQ2 p.Arg147His Pathogenic/Likely pathogenic ★★ same condition
COQ2 p.Ser96Asn Pathogenic ★★ same condition
COQ2 p.Trp24Ter Likely pathogenic ★★ same condition
COQ2 c.-26G>C Uncertain significance ★★ same condition
COQ2 p.Ala100Thr Uncertain significance ★★ ⚠ same condition
COQ2 p.Ala14Ser Uncertain significance ★★ same condition
COQ2 p.Ala151Thr Uncertain significance ★★ ⚠ 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/coq2-p-pro20ser (accessed [today's date]).

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