Is COX20 p.Leu39= (c.115T>C) pathogenic?

COX20 p.Leu39= (c.115T>C) is classified Likely benign in COX20 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-17). Absent from gnomAD v4.1; Associated with mitochondrial complex IV deficiency, nuclear type 11.

What condition is associated with COX20 p.Leu39= (c.115T>C)?

COX20 p.Leu39= (c.115T>C) is associated with mitochondrial complex IV deficiency, nuclear type 11 (ClinVar).

How common is COX20 p.Leu39= (c.115T>C) in the general population?

COX20 p.Leu39= (c.115T>C) is absent from gnomAD v4.1 (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.Leu39=

c.115T>C · rs1573315547 · VCV798926

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -3.8
Overall
CADD	5.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COX20
Protein: p.Leu39=
Coding: c.115T>C
MANE Select: NM_198076
dbSNP: rs1573315547
Type: single nucleotide variant
Location: chr1:244842016 (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 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
COX20 p.Cys59Arg 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-leu39 (accessed [today's date]).

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