TBCK p.Pro738=
c.2214A>G · rs538674033 · VCV724560
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.094%, sas)
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 -0.85 | GERP -3.5, phastCons 0.013 |
| Overall | ||
| CADD | 5.565 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.094%
South Asian · 85/90,404 alleles
Filtering AF
0.0778%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0719%
Overall
0.011%
177/1,610,130 alleles · ultra-rare
exomes 158/1,457,890 · genomes 19/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.094% | 1,064 |
| Admixed American | 0.0187% | 5,335 |
| Middle Eastern | 0.0166% | 6,034 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,795 |
| European (non-Finnish) | 0.00568% | 17,593 |
| African / African-American | 0.00535% | 18,690 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,476 |
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.Pro738=
- Coding
- c.2214A>G
- MANE Select
- NM_001163435
- dbSNP
- rs538674033
- Type
- single nucleotide variant
- Location
- chr4:106171116 (GRCh38)
- Gene constraint
- LOEUF 1.062 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
- Residue 738
- the 'disordered' region
Similar variants
- TBCK p.Pro738Leu Uncertain significance ★★ ⚠ same residue
- TBCK p.Pro738Ser 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-pro738 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown