Is COQ2 p.Ser280= (c.840C>T) pathogenic?

COQ2 p.Ser280= (c.840C>T) is classified Benign in COQ2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 30.1%, mid) — too common for a highly-penetrant pathogenic allele; Associated with coenzyme Q10 deficiency, primary, 1.

What condition is associated with COQ2 p.Ser280= (c.840C>T)?

COQ2 p.Ser280= (c.840C>T) is associated with coenzyme Q10 deficiency, primary, 1 (ClinVar).

COQ2 p.Ser280=

Q: How common is COQ2 p.Ser280= (c.840C>T) in the general population?

COQ2 p.Ser280= (c.840C>T) is common (popmax 30.1%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.840C>T · rs1129617 · VCV128830

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 30.1%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

coenzyme Q10 deficiency, primary, 1

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 -0.91	GERP -2.8
Overall
CADD	3.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.1% Middle Eastern · 1,791/5,958 alleles

Filtering AF 28.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.4%

Overall 26.9% 417,982/1,554,922 alleles · common exomes 383,173/1,402,898 · genomes 34,809/152,024 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	32.2%	3
Middle Easterngrpmax	30.1%	3
Admixed American	28.4%	4
European (non-Finnish)	28.2%	4
South Asian	28.2%	4
Remaining individualsnot grpmax-eligible	26.6%	4
Amishnot grpmax-eligible	23%	4
Finnishnot grpmax-eligible	20.9%	5
East Asian	13.7%	7
African / African-American	13.5%	7

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: COQ2
Protein: p.Ser280=
Coding: c.840C>T
MANE Select: NM_001358921
dbSNP: rs1129617
Type: single nucleotide variant
Location: chr4:83267697 (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.Ser280Arg Uncertain significance ★★ ⚠ same residue
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

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-ser280 (accessed [today's date]).

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