TBCK p.Asp6=
c.18C>T · rs139587868 · VCV1123237
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.479%, mid)
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 2.2 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 13.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.479%
Middle Eastern · 29/6,056 alleles
Filtering AF
0.343%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.296%
Overall
0.0695%
1,121/1,613,822 alleles · rare
exomes 1,029/1,461,640 · genomes 92/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.479% | 209 |
| Ashkenazi Jewishnot grpmax-eligible | 0.179% | 558 |
| Admixed American | 0.108% | 923 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| European (non-Finnish) | 0.0724% | 1,382 |
| South Asian | 0.0615% | 1,626 |
| African / African-American | 0.0133% | 7,497 |
| Finnishnot grpmax-eligible | 0.00156% | 64,010 |
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
- TBCK
- Protein
- p.Asp6=
- Coding
- c.18C>T
- MANE Select
- NM_001163435
- dbSNP
- rs139587868
- Type
- single nucleotide variant
- Location
- chr4:106308943 (GRCh38)
- Gene constraint
- LOEUF 1.062 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
- Residue 6
- the protein kinase domain
Similar variants
- 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
- TBCK c.2060-2A>G Pathogenic/Likely pathogenic ★★ same type
- TBCK c.266+2T>G 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/tbck-p-asp6 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown