Is TK2 p.Leu161Arg (c.482T>G) pathogenic?

TK2 p.Leu161Arg (c.482T>G) is classified Uncertain significance in TK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely pathogenic (0.912); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TK2 p.Leu161Arg (c.482T>G)?

TK2 p.Leu161Arg (c.482T>G) is associated with Inborn genetic diseases (ClinVar).

How common is TK2 p.Leu161Arg (c.482T>G) in the general population?

TK2 p.Leu161Arg (c.482T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TK2 p.Leu161Arg (c.482T>G)?

AlphaMissense predicts likely pathogenic (score 0.912) — an in-silico prediction, not a clinical call.

TK2 p.Leu161Arg

c.482T>G · VCV4184898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.912 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.912	likely pathogenic
REVEL	0.748	pathogenic-leaning
SaProt	LLR -15.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.69, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 38 kb · p 0.097 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TK2
Protein: p.Leu161Arg
Coding: c.482T>G
MANE Select: NM_004614
Type: single nucleotide variant
Location: chr16:66517845 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TK2 p.Leu161= Likely benign ★ same residue
TK2 p.Ala229Pro Uncertain significance ★★ ⚠ same condition
TK2 p.Arg123His Uncertain significance ★★ ⚠ same condition
TK2 p.Arg252Gln Uncertain significance ★★ ⚠ same condition
TK2 p.Arg261Gln Uncertain significance ★★ ⚠ same condition
TK2 p.Arg261Leu Uncertain significance ★★ ⚠ same condition
TK2 p.Gln110Arg Uncertain significance ★★ ⚠ same condition
TK2 p.Glu246Val Uncertain significance ★★ ⚠ 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-leu161arg (accessed [today's date]).

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