Is TK2 p.Lys202del (c.604_606del) pathogenic?

TK2 p.Lys202del (c.604606del) is classified Pathogenic/Likely pathogenic in TK2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-24). Very rare (popmax 0.00666%, amr); Associated with mitochondrial DNA depletion syndrome.

What condition is associated with TK2 p.Lys202del (c.604_606del)?

TK2 p.Lys202del (c.604_606del) is associated with mitochondrial DNA depletion syndrome, mitochondrial DNA depletion syndrome, myopathic form, mitochondrial disease (ClinVar).

How common is TK2 p.Lys202del (c.604_606del) in the general population?

TK2 p.Lys202del (c.604_606del) is very rare (popmax 0.00666%, amr) (gnomAD).

TK2 p.Lys202del

c.604_606del · rs281865501 · VCV38995

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Conditions

mitochondrial DNA depletion syndrome

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 -0.023	GERP -0.67, phastCons 0.001
Overall
CADD	19.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,028 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00217% 35/1,614,174 alleles · very rare exomes 30/1,461,850 · genomes 5/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,007
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00267%	37,518
European (non-Finnish)	0.00229%	43,704

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: TK2
Protein: p.Lys202del
Coding: c.604_606del
MANE Select: NM_004614
dbSNP: rs281865501
Type: Deletion
Location: chr16:66517148 (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 DNA depletion syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial DNA depletion syndrome, myopathic form mitochondrial disease

Similar variants

TK2 c.536_538+8del Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Leu182fs 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 p.Lys202Arg Uncertain significance ★ ⚠ same residue
TK2 c.156+2T>C 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-lys202del (accessed [today's date]).

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