Is TK2 c.*342C>A pathogenic?

TK2 c.342C>A is classified Uncertain significance in TK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0262%, sas); Associated with mitochondrial DNA depletion syndrome, myopathic form.

What condition is associated with TK2 c.*342C>A?

TK2 c.*342C>A is associated with mitochondrial DNA depletion syndrome, myopathic form (ClinVar).

How common is TK2 c.*342C>A in the general population?

TK2 c.*342C>A is ultra-rare (popmax 0.0262%, sas) (gnomAD).

TK2 c.*342C>A

Q: How is Mitochondrial DNA depletion syndrome, myopathic form inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs544189950 · VCV320156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, sas)

Conditions

mitochondrial DNA depletion syndrome, myopathic form

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 -2.2	GERP -2.9
Non-coding constraint	Z 1.48	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	1.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0262% South Asian · 12/45,832 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00478% 19/397,894 alleles · ultra-rare exomes 13/245,576 · genomes 6/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0262%	3,819
European (non-Finnish)	0.00286%	34,971
African / African-American	0.00205%	48,736

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
Coding: c.*342C>A
MANE Select: NM_004614
dbSNP: rs544189950
Type: single nucleotide variant
Location: chr16:66511626 (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, myopathic form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mitochondrial DNA depletion syndrome, myopathic form (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TK2 p.Ala139Thr Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Ala139Val Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Arg130Trp Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Arg183Trp Pathogenic ★★ ⚠ same condition
TK2 p.Arg192Lys Pathogenic ★★ same condition
TK2 p.Asn58Ser Pathogenic/Likely pathogenic ★★ same condition
TK2 p.Gln110Ter 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-c-star-342c-a (accessed [today's date]).

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