TK2 p.Thr64=
c.192G>A · rs373843440 · VCV1554864
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.029%, eas)
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 -7.1 | GERP -3.9 |
| Overall | ||
| CADD | 5.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.029%
East Asian · 13/44,884 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00341%
55/1,614,092 alleles · ultra-rare
exomes 42/1,461,852 · genomes 13/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.029% | 3,453 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| South Asian | 0.0121% | 8,281 |
| African / African-American | 0.012% | 8,334 |
| European (non-Finnish) | 0.000763% | 131,110 |
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.Thr64=
- Coding
- c.192G>A
- MANE Select
- NM_004614
- dbSNP
- rs373843440
- Type
- single nucleotide variant
- Location
- chr16:66541918 (GRCh38)
- Gene constraint
- LOEUF 1.101 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.01
- Residue 64
- a UniProt-annotated variant site (in mtdps2); a binding site
Similar variants
- TK2 p.Thr64Met Pathogenic/Likely pathogenic ★★ 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
- TK2 p.Arg130Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- TK2 p.Arg130Trp 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-thr64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown