Is TK2 c.*615A>C pathogenic?

TK2 c.615A>C is classified Uncertain significance in TK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). No allele count reported in gnomAD v4.1 (AN 163,566); Associated with mitochondrial DNA depletion syndrome, myopathic form.

What condition is associated with TK2 c.*615A>C?

TK2 c.*615A>C is associated with mitochondrial DNA depletion syndrome, myopathic form (ClinVar).

How common is TK2 c.*615A>C in the general population?

TK2 c.*615A>C is no allele count reported in gnomAD v4.1 (AN 163,566) (gnomAD).

TK2 c.*615A>C

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

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

rs886052208 · VCV320151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 163,566)

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 -2.7	GERP -2.9
Non-coding constraint	Z 1.48	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	0.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 163,566). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TK2
Coding: c.*615A>C
MANE Select: NM_004614
dbSNP: rs886052208
Type: single nucleotide variant
Location: chr16:66511353 (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-615a-c (accessed [today's date]).

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