TK2 p.Phe248=
c.744T>C · rs147834546 · VCV702829
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0853%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor gain, 44 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.22 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -3.9, phastCons 1 |
| Overall | ||
| CADD | 8.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0853%
African / African-American · 64/75,052 alleles
Filtering AF
0.0685%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0624%
Overall
0.00415%
67/1,614,214 alleles · ultra-rare
exomes 29/1,461,892 · genomes 38/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0853% | 1,173 |
| Admixed American | 0.00167% | 60,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
| European (non-Finnish) | 8.47e-05% | 1,180,045 |
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.Phe248=
- Coding
- c.744T>C
- MANE Select
- NM_004614
- dbSNP
- rs147834546
- Type
- single nucleotide variant
- Location
- chr16:66512022 (GRCh38)
- Gene constraint
- LOEUF 1.101 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.01
Similar variants
- 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
- TK2 p.Arg183Gly 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-phe248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown