Is TK2 p.Gln125Ter (c.372_373delinsCT) pathogenic?

TK2 p.Gln125Ter (c.372373delinsCT) is classified Pathogenic in TK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-08). No gnomAD frequency available for this variant; Associated with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3.

How common is TK2 p.Gln125Ter (c.372_373delinsCT) in the general population?

TK2 p.Gln125Ter (c.372_373delinsCT) is no gnomAD frequency available for this variant (gnomAD).

TK2 p.Gln125Ter

Q: What condition is associated with TK2 p.Gln125Ter (c.372_373delinsCT)?

TK2 p.Gln125Ter (c.372_373delinsCT) is associated with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, mitochondrial DNA depletion syndrome, myopathic form, mitochondrial disease (ClinVar).

Q: How is Autosomal recessive progressive external ophthalmoplegia inherited?

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

c.372_373delinsCT · rs886039669 · VCV265614

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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
Protein: p.Gln125Ter
Coding: c.372_373delinsCT
MANE Select: NM_004614
dbSNP: rs886039669
Type: Indel
Location: chr16:66531382 (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

progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Autosomal recessive progressive external ophthalmoplegia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

TK2 p.Gln125His Uncertain significance ★★ same residue
TK2 c.156+2T>C Pathogenic/Likely pathogenic ★★ same condition
TK2 c.157-2A>G Pathogenic/Likely pathogenic ★★ same condition
TK2 c.536_538+8del Pathogenic/Likely pathogenic ★★ same condition
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.Arg130Gln 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-gln125ter (accessed [today's date]).

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