Is COX14 p.Glu50= (c.150A>G) pathogenic?

COX14 p.Glu50= (c.150A>G) is classified Likely benign in COX14 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-14). Ultra-rare (popmax 0.0142%, nfe); Associated with mitochondrial complex IV deficiency, nuclear type 10.

What condition is associated with COX14 p.Glu50= (c.150A>G)?

COX14 p.Glu50= (c.150A>G) is associated with mitochondrial complex IV deficiency, nuclear type 10 (ClinVar).

How common is COX14 p.Glu50= (c.150A>G) in the general population?

COX14 p.Glu50= (c.150A>G) is ultra-rare (popmax 0.0142%, 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.

COX14 p.Glu50=

c.150A>G · rs372336241 · VCV559379

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Conditions

mitochondrial complex IV deficiency, nuclear type 10

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 0.17	GERP -3.4, phastCons 0.16
Overall
CADD	5.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0142% European (non-Finnish) · 168/1,180,018 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0107% 173/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0142%	7,024
African / African-American	0.004%	25,011
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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: COX14
Protein: p.Glu50=
Coding: c.150A>G
MANE Select: NM_032901
dbSNP: rs372336241
Type: single nucleotide variant
Location: chr12:50120193 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 86.03

Full COX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 10 — 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

COX14 p.Glu50Lys Uncertain significance ★ ⚠ same residue
COX14 p.Ser54Pro Uncertain significance ★★ ⚠ same condition
COX14 p.Tyr25Cys Uncertain significance ★★ ⚠ same condition
COX14 c.-8-14A>G Likely benign ★★ same condition
COX14 p.Met19Ile Pathogenic ⚠ same condition
COX14 p.Arg41Cys Uncertain significance ★★ ⚠ same type
COX14 p.Met1Ile Uncertain significance ★★ same type
COX14 p.Thr3Ala Uncertain significance ★★ ⚠ 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/cox14-p-glu50 (accessed [today's date]).

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