Is COX10 p.Phe413del (c.1235TCT[1]) pathogenic?

COX10 p.Phe413del (c.1235TCT[1]) is classified Uncertain significance in COX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-22). Very rare (popmax 0.004%, afr); Associated with mitochondrial complex IV deficiency, nuclear type 3.

What condition is associated with COX10 p.Phe413del (c.1235TCT[1])?

COX10 p.Phe413del (c.1235TCT[1]) is associated with mitochondrial complex IV deficiency, nuclear type 3 (ClinVar).

How common is COX10 p.Phe413del (c.1235TCT[1]) in the general population?

COX10 p.Phe413del (c.1235TCT[1]) is very rare (popmax 0.004%, 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.Phe413del

c.1235TCT[1] · VCV3581680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

mitochondrial complex IV deficiency, nuclear type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.74	GERP -1, phastCons 1
Overall
CADD	18.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,050 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000744% 12/1,613,306 alleles · very rare exomes 9/1,460,980 · genomes 3/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,017
South Asian	0.0022%	45,534
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00158%	63,388
European (non-Finnish)	0.000424%	235,976

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.Phe413del
Coding: c.1235TCT[1]
MANE Select: NM_001303
Type: Microsatellite
Location: chr17:14207115 (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 3 — 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

COX10 p.Cys243del Uncertain significance ★★ same condition
COX10 p.Leu425_Met426insLeu Uncertain significance ★ same condition
COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same condition
COX10 p.Gln230Ter Likely pathogenic ★★ same condition
COX10 p.Pro225Leu Likely pathogenic ★★ same condition
COX10 c.-89G>C Uncertain significance ★★ same condition
COX10 c.-89G>T Uncertain significance ★★ same condition
COX10 p.Ala174Thr 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-phe413del (accessed [today's date]).

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