TK2 p.Cys197=
c.591C>T · rs528776721 · VCV1443525
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor loss, 27 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.25 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.54, phastCons 1 |
| Overall | ||
| CADD | 12.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,882 alleles
Filtering AF
0.00434%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.000805%
13/1,614,152 alleles · ultra-rare
exomes 10/1,461,862 · genomes 3/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,976 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| South Asian | 0.0022% | 45,544 |
| Admixed American | 0.00167% | 60,012 |
| European (non-Finnish) | 8.47e-05% | 1,180,016 |
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.Cys197=
- Coding
- c.591C>T
- MANE Select
- NM_004614
- dbSNP
- rs528776721
- Type
- single nucleotide variant
- Location
- chr16:66517163 (GRCh38)
- Gene constraint
- LOEUF 1.101 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.01
Similar variants
- TK2 p.Cys197Arg Uncertain significance ★ ⚠ 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-cys197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown