Is TACO1 p.Pro22= (c.66C>T) pathogenic?

TACO1 p.Pro22= (c.66C>T) is classified Likely benign in TACO1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-24). Ultra-rare (popmax 0.0197%, amr); Associated with mitochondrial complex IV deficiency, nuclear type 8.

What condition is associated with TACO1 p.Pro22= (c.66C>T)?

TACO1 p.Pro22= (c.66C>T) is associated with mitochondrial complex IV deficiency, nuclear type 8 (ClinVar).

How common is TACO1 p.Pro22= (c.66C>T) in the general population?

TACO1 p.Pro22= (c.66C>T) is ultra-rare (popmax 0.0197%, amr) (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.

TACO1 p.Pro22=

c.66C>T · rs1008008624 · VCV736395

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, amr)

Conditions

mitochondrial complex IV deficiency, nuclear type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.34	GERP -1.8
Overall
CADD	7.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% Admixed American · 10/50,858 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00104% 16/1,544,060 alleles · ultra-rare exomes 9/1,391,770 · genomes 7/152,290 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0197%	5,086
Remaining individualsnot grpmax-eligible	0.00335%	29,879
African / African-American	0.00137%	73,018
European (non-Finnish)	0.000262%	381,780

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: TACO1
Protein: p.Pro22=
Coding: c.66C>T
MANE Select: NM_016360
dbSNP: rs1008008624
Type: single nucleotide variant
Location: chr17:63601149 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.91 · 8 PDB
Residue 22: the 'disordered' region

Full TACO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 8 — 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

TACO1 c.280+1G>C Pathogenic/Likely pathogenic ★★ same condition
TACO1 p.Arg141Ter Pathogenic ★★ same condition
TACO1 p.Arg113His Uncertain significance ★★ ⚠ same condition
TACO1 p.Arg141Gln Uncertain significance ★★ ⚠ same condition
TACO1 p.Arg205Cys Uncertain significance ★★ ⚠ same condition
TACO1 p.Arg89Cys Uncertain significance ★★ ⚠ same condition
TACO1 p.Asn171His Uncertain significance ★★ ⚠ same condition
TACO1 p.Glu151Gly 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/taco1-p-pro22 (accessed [today's date]).

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