Is COX20 p.Glu6Ter (c.16G>T) pathogenic?

COX20 p.Glu6Ter (c.16G>T) is classified Likely pathogenic in COX20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). Very rare (popmax 9.95e-05%, nfe); Associated with mitochondrial complex IV deficiency, nuclear type 11.

What condition is associated with COX20 p.Glu6Ter (c.16G>T)?

COX20 p.Glu6Ter (c.16G>T) is associated with mitochondrial complex IV deficiency, nuclear type 11 (ClinVar).

How common is COX20 p.Glu6Ter (c.16G>T) in the general population?

COX20 p.Glu6Ter (c.16G>T) is very rare (popmax 9.95e-05%, nfe) (gnomAD).

How is Isolated cytochrome C oxidase deficiency inherited?

Typically Autosomal recessive, Mitochondrial inheritance (Orphanet). A genetic counselor can assess individual risk for a family.

COX20 p.Glu6Ter

c.16G>T · VCV3582926

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.95e-05%, nfe)

Conditions

mitochondrial complex IV deficiency, nuclear type 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 0.69, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.95e-05% European (non-Finnish) · 1/1,005,080 alleles

Overall 8.94e-05% 1/1,118,290 alleles · very rare

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: COX20
Protein: p.Glu6Ter
Coding: c.16G>T
MANE Select: NM_198076
Type: single nucleotide variant
Location: chr1:244835730 (GRCh38)
Gene constraint: LOEUF 1.927 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.42

Full COX20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

COX20 p.Glu6= Likely benign ★ same residue
COX20 c.157+3G>C Pathogenic/Likely pathogenic ★★ same condition
COX20 p.Lys14Arg Pathogenic ★★ ⚠ same condition
COX20 p.Tyr36Ter Likely pathogenic ★★ same condition
COX20 p.Ala3Thr Uncertain significance ★★ ⚠ same condition
COX20 p.Arg31Trp Uncertain significance ★★ ⚠ same condition
COX20 p.Asp107Asn Uncertain significance ★★ ⚠ same condition
COX20 p.Asp107His 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/cox20-p-glu6ter (accessed [today's date]).

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