Is COQ2 p.Val348= (c.1044C>T) pathogenic?

COQ2 p.Val348= (c.1044C>T) is classified Likely benign in COQ2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-22). Rare (popmax 0.142%, afr); Associated with multiple system atrophy 1, susceptibility to.

How common is COQ2 p.Val348= (c.1044C>T) in the general population?

COQ2 p.Val348= (c.1044C>T) is rare (popmax 0.142%, afr) (gnomAD).

COQ2 p.Val348=

Q: What condition is associated with COQ2 p.Val348= (c.1044C>T)?

COQ2 p.Val348= (c.1044C>T) is associated with multiple system atrophy 1, susceptibility to, coenzyme Q10 deficiency, primary, 1 (ClinVar).

c.1044C>T · rs6834269 · VCV384976

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.142%, afr)

Conditions

multiple system atrophy 1, susceptibility to

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 0.26	GERP -3.4, phastCons 0.93
Overall
CADD	0.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% African / African-American · 106/74,624 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.00937% 151/1,610,706 alleles · rare exomes 69/1,459,114 · genomes 82/151,592 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.142%	704
Admixed American	0.047%	2,127
Middle Eastern	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.0209%	4,796
European (non-Finnish)	0.00017%	589,324

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.Val348=
Coding: c.1044C>T
MANE Select: NM_001358921
dbSNP: rs6834269
Type: single nucleotide variant
Location: chr4:83264271 (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

multiple system atrophy 1, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: coenzyme Q10 deficiency, primary, 1

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-val348 (accessed [today's date]).

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