TBCK p.Asp407=
c.1221C>T · VCV3895941
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000266%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 0.31, phastCons 1 |
| Overall | ||
| CADD | 14.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000266%
European (non-Finnish) · 3/1,127,736 alleles
Filtering AF
7.1e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2e-05%
Overall
0.0002%
3/1,498,116 alleles · very rare
exomes 3/1,347,912 · genomes 0/150,204 · joint denominator
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.Asp407=
- Coding
- c.1221C>T
- MANE Select
- NM_001163435
- Type
- single nucleotide variant
- Location
- chr4:106236519 (GRCh38)
- Gene constraint
- LOEUF 1.062 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
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-asp407 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown