Is COX10 p.Leu64= (c.192G>A) pathogenic?

COX10 p.Leu64= (c.192G>A) is classified Conflicting classifications of pathogenicity in COX10 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-04). Ultra-rare (popmax 0.068%, afr); Associated with mitochondrial complex IV deficiency, nuclear type 1.

What condition is associated with COX10 p.Leu64= (c.192G>A)?

COX10 p.Leu64= (c.192G>A) is associated with mitochondrial complex IV deficiency, nuclear type 1, Leigh syndrome (ClinVar).

How common is COX10 p.Leu64= (c.192G>A) in the general population?

COX10 p.Leu64= (c.192G>A) is ultra-rare (popmax 0.068%, afr) (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.

COX10 p.Leu64=

c.192G>A · rs569444237 · VCV321813

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.068%, afr)

Conditions

mitochondrial complex IV deficiency, nuclear type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.086	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.26, phastCons 1
Overall
CADD	8.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.068% African / African-American · 51/75,034 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00328% 53/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.068%	1,471
Admixed American	0.00167%	60,022
European (non-Finnish)	8.47e-05%	1,180,025

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: COX10
Protein: p.Leu64=
Coding: c.192G>A
MANE Select: NM_001303
dbSNP: rs569444237
Type: single nucleotide variant
Location: chr17:14076749 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11

Full COX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leigh syndrome

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same condition
COX10 c.-89G>C Uncertain significance ★★ same condition
COX10 c.-89G>T Uncertain significance ★★ same condition
COX10 p.Ala390Val Uncertain significance ★★ ⚠ same condition
COX10 p.Arg354Gln Uncertain significance ★★ ⚠ same condition
COX10 p.Arg355His Uncertain significance ★★ ⚠ same condition
COX10 p.Arg398Cys Uncertain significance ★★ ⚠ same condition
COX10 p.Asp132Tyr 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/cox10-p-leu64 (accessed [today's date]).

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