Is TK2 p.Leu182fs (c.544del) pathogenic?

TK2 p.Leu182fs (c.544del) is classified Pathogenic/Likely pathogenic in TK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Associated with mitochondrial disease.

TK2 p.Leu182fs

Q: What condition is associated with TK2 p.Leu182fs (c.544del)?

TK2 p.Leu182fs (c.544del) is associated with mitochondrial disease, mitochondrial DNA depletion syndrome, myopathic form, progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 (ClinVar).

c.544del · VCV3581130

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

mitochondrial disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: TK2
Protein: p.Leu182fs
Coding: c.544del
MANE Select: NM_004614
Type: Deletion
Location: chr16:66517210 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01

Full TK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial DNA depletion syndrome, myopathic form progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3

Similar variants

TK2 c.536_538+8del Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Lys202del Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Lys43fs Pathogenic ★★ same condition
TK2 p.Tyr148fs Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Ile168fs Pathogenic ★ same condition
TK2 p.Asp42_Lys43delinsGlu Conflicting classifications of pathogenicity ★ same condition
TK2 c.156+2T>C Pathogenic/Likely pathogenic ★★ same condition
TK2 c.157-2A>G Pathogenic/Likely pathogenic ★★ 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/tk2-p-leu182fs (accessed [today's date]).

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