Is TACO1 p.Pro99= (c.297T>G) pathogenic?

TACO1 p.Pro99= (c.297T>G) is classified Conflicting classifications of pathogenicity in TACO1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-11-19). Very rare (popmax 0.00373%, nfe); Associated with mitochondrial complex IV deficiency, nuclear type 1.

What condition is associated with TACO1 p.Pro99= (c.297T>G)?

TACO1 p.Pro99= (c.297T>G) is associated with mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

How common is TACO1 p.Pro99= (c.297T>G) in the general population?

TACO1 p.Pro99= (c.297T>G) is very rare (popmax 0.00373%, 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.

TACO1 p.Pro99=

c.297T>G · rs778960378 · VCV324444

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -2.4, phastCons 0.046
Overall
CADD	8.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,180,006 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00297% 48/1,613,990 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,818
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,453

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.Pro99=
Coding: c.297T>G
MANE Select: NM_016360
dbSNP: rs778960378
Type: single nucleotide variant
Location: chr17:63604550 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.91 · 8 PDB

Full TACO1 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

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

TACO1 p.Asn171His Uncertain significance ★★ ⚠ same condition
TACO1 p.Lys159Arg Uncertain significance ★★ ⚠ same condition
TACO1 p.Val292Ile Uncertain significance ★★ ⚠ same condition
TACO1 c.*343C>T Likely benign ★★ same condition
TACO1 p.Gly145Ser Benign ★★ ⚠ same condition
TACO1 c.515+11G>A Uncertain significance ★ same condition
TACO1 c.-163A>G Uncertain significance ★ same condition
TACO1 c.-168A>G 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-pro99 (accessed [today's date]).

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