TK2 p.Arg183=
c.547C>A · rs137886900 · VCV1208662
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.45 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.35 | loss · gain 0.16 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 22.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/75,034 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00136%
22/1,614,038 alleles · ultra-rare
exomes 4/1,461,794 · genomes 18/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,573 |
| Admixed American | 0.00167% | 60,010 |
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.Arg183=
- Coding
- c.547C>A
- MANE Select
- NM_004614
- dbSNP
- rs137886900
- Type
- single nucleotide variant
- Location
- chr16:66517207 (GRCh38)
- Gene constraint
- LOEUF 1.101 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.01
- Residue 183
- a UniProt-annotated variant site (in mtdps2 and peob3; reduction of activity; reduced affinity for atp)
Similar variants
- TK2 p.Arg183Gly Pathogenic/Likely pathogenic ★★ same residue
- TK2 p.Arg183Trp Pathogenic ★★ ⚠ same residue
- TK2 p.Arg183Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg183 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown