TBCK p.Ala71=
c.213T>G · rs370925445 · VCV2192170
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, nfe)
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 -0.8 | GERP -3.2 |
| Overall | ||
| CADD | 7.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
European (non-Finnish) · 59/1,179,670 alleles
Filtering AF
0.00394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00361%
Overall
0.00372%
60/1,613,370 alleles · very rare
exomes 59/1,461,146 · genomes 1/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.005% | 19,994 |
| African / African-American | 0.00134% | 74,906 |
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.Ala71=
- Coding
- c.213T>G
- MANE Select
- NM_001163435
- dbSNP
- rs370925445
- Type
- single nucleotide variant
- Location
- chr4:106295147 (GRCh38)
- Gene constraint
- LOEUF 1.062 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
- Residue 71
- 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-ala71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown