TBCK p.Arg85=
c.255G>A · rs373691598 · VCV1608215
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
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 1.4 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 11.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,870 alleles
Filtering AF
0.00624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.000744%
12/1,613,060 alleles · ultra-rare
exomes 7/1,460,904 · genomes 5/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,319 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,215 |
| European (non-Finnish) | 8.48e-05% | 1,179,422 |
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.Arg85=
- Coding
- c.255G>A
- MANE Select
- NM_001163435
- dbSNP
- rs373691598
- Type
- single nucleotide variant
- Location
- chr4:106295105 (GRCh38)
- Gene constraint
- LOEUF 1.062 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
- Residue 85
- the protein kinase domain
Similar variants
- TBCK p.Arg85fs Pathogenic ★ 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
- TBCK c.2060-2A>G 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/tbck-p-arg85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown