Is COQ2 p.Val63= (c.189G>T) pathogenic?

COQ2 p.Val63= (c.189G>T) is classified Benign/Likely benign in COQ2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.23%, afr); Associated with focal segmental glomerulosclerosis.

What condition is associated with COQ2 p.Val63= (c.189G>T)?

COQ2 p.Val63= (c.189G>T) is associated with focal segmental glomerulosclerosis (ClinVar).

How common is COQ2 p.Val63= (c.189G>T) in the general population?

COQ2 p.Val63= (c.189G>T) is low-frequency (popmax 2.23%, afr) (gnomAD).

COQ2 p.Val63=

c.189G>T · rs368507578 · VCV136980

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.23%, afr)

Conditions

focal segmental glomerulosclerosis

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 -13	GERP -3.2
Overall
CADD	0.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.23% African / African-American · 1,597/71,712 alleles

Filtering AF 2.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1%

Overall 0.124% 1,922/1,553,630 alleles · low-frequency exomes 930/1,401,452 · genomes 992/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.23%	45
Middle Eastern	0.19%	527
Admixed American	0.181%	553
Remaining individualsnot grpmax-eligible	0.146%	684
European (non-Finnish)	0.0112%	8,924
South Asian	0.00356%	28,119

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.Val63=
Coding: c.189G>T
MANE Select: NM_001358921
dbSNP: rs368507578
Type: single nucleotide variant
Location: chr4:83284576 (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

focal segmental glomerulosclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COQ2 p.Val63Ala Uncertain significance ★ ⚠ same residue
COQ2 p.Arg22Ter Benign/Likely benign ★★ same condition
COQ2 p.Asp65Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
COQ2 p.Ala17fs Conflicting classifications of pathogenicity ★ same condition
COQ2 p.Arg123Cys Likely pathogenic ★★ same type
COQ2 p.Arg147His Pathogenic/Likely pathogenic ★★ same type
COQ2 p.Gln44Ter Likely pathogenic ★★ same type
COQ2 p.Ser96Asn Pathogenic ★★ same type

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-val63 (accessed [today's date]).

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