Is TK2 p.Asn93Lys (c.279T>A) pathogenic?

TK2 p.Asn93Lys (c.279T>A) is classified Uncertain significance in TK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-17). AlphaMissense: likely pathogenic (0.9449); Absent from gnomAD v4.1.

How common is TK2 p.Asn93Lys (c.279T>A) in the general population?

TK2 p.Asn93Lys (c.279T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TK2 p.Asn93Lys (c.279T>A)?

AlphaMissense predicts likely pathogenic (score 0.9449) — an in-silico prediction, not a clinical call.

TK2 p.Asn93Lys

c.279T>A · rs2507165538 · VCV2092149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9449 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9449	likely pathogenic · top 7% in TK2
REVEL	0.604	indeterminate
SaProt	LLR -14.26	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.51	GERP -0.6, phastCons 0.8
Regional constraint	o/e 0.91	unconstrained · MANE · 38 kb · p 0.097 · regional, not allelic
Overall
CADD	21.7	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.Asn93Lys
Coding: c.279T>A
MANE Select: NM_004614
dbSNP: rs2507165538
Type: single nucleotide variant
Location: chr16:66536970 (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

Similar variants

TK2 p.Asn93Asp Uncertain significance ★ same residue
TK2 p.Asn93Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TK2 p.Asn93= Likely benign ★ same residue
TK2 c.156+2T>C Pathogenic/Likely pathogenic ★★ same type
TK2 c.157-2A>G Pathogenic/Likely pathogenic ★★ same type
TK2 p.Ala139Thr Pathogenic/Likely pathogenic ★★ same type
TK2 p.Ala139Val Pathogenic/Likely pathogenic ★★ same type
TK2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ same type

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-asn93lys (accessed [today's date]).

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