TBCK p.Arg66=
c.198A>G · rs748075983 · VCV1589795
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0017%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 8.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0017%
Admixed American · 1/58,660 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000311%
5/1,610,204 alleles · very rare
exomes 5/1,457,898 · genomes 0/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0017% | 58,660 |
| European (non-Finnish) | 0.000339% | 294,718 |
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
- TBCK
- Protein
- p.Arg66=
- Coding
- c.198A>G
- MANE Select
- NM_001163435
- dbSNP
- rs748075983
- Type
- single nucleotide variant
- Location
- chr4:106295162 (GRCh38)
- Gene constraint
- LOEUF 1.062 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
- Residue 66
- the protein kinase domain; a UniProt-annotated variant site (in)
Similar variants
- TBCK p.Arg66Ter Pathogenic/Likely pathogenic ★★ same residue
- TBCK p.Arg66Leu Uncertain significance ★ ⚠ same residue
- TBCK c.1170+1G>A Pathogenic/Likely pathogenic ★★ same type
- TBCK c.1351-1G>A Likely pathogenic ★★ same type
- TBCK c.1775-1G>C Likely pathogenic ★★ same type
- TBCK c.1860+1G>A Pathogenic ★★ same type
- TBCK c.1897+1G>A Pathogenic ★★ same type
- TBCK c.193+1G>T 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/tbck-p-arg66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown