Is TK2 p.Asp173= (c.519C>T) pathogenic?

TK2 p.Asp173= (c.519C>T) is classified Conflicting classifications of pathogenicity in TK2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.049%, eas); Associated with mitochondrial DNA depletion syndrome, myopathic form.

What condition is associated with TK2 p.Asp173= (c.519C>T)?

TK2 p.Asp173= (c.519C>T) is associated with mitochondrial DNA depletion syndrome, myopathic form (ClinVar).

How common is TK2 p.Asp173= (c.519C>T) in the general population?

TK2 p.Asp173= (c.519C>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

TK2 p.Asp173=

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

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

c.519C>T · rs143378852 · VCV887485

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6	GERP -3.6
Overall
CADD	0.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.049% East Asian · 22/44,856 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00366% 59/1,613,916 alleles · ultra-rare exomes 56/1,461,818 · genomes 3/152,098 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,039
African / African-American	0.00534%	18,723
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.00246%	40,689
Admixed American	0.00167%	60,000

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.Asp173=
Coding: c.519C>T
MANE Select: NM_004614
dbSNP: rs143378852
Type: single nucleotide variant
Location: chr16:66517808 (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-p-asp173 (accessed [today's date]).

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