TBCD p.Ser598=
c.1794C>T · rs374405509 · VCV1557643
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.108%, sas)
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 -7.4 | GERP -4.6 |
| Overall | ||
| CADD | 0.816 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.108%
South Asian · 95/87,600 alleles
Filtering AF
0.0908%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0842%
Overall
0.0103%
165/1,595,346 alleles · rare
exomes 128/1,443,004 · genomes 37/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.108% | 922 |
| African / African-American | 0.0709% | 1,410 |
| Remaining individualsnot grpmax-eligible | 0.00648% | 15,438 |
| East Asian | 0.00228% | 43,936 |
| European (non-Finnish) | 0.00102% | 97,583 |
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
- TBCD
- Protein
- p.Ser598=
- Coding
- c.1794C>T
- MANE Select
- NM_005993
- dbSNP
- rs374405509
- Type
- single nucleotide variant
- Location
- chr17:82903468 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.45 · 6 PDB
Similar variants
- TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same type
- TBCD c.2007-2A>G Likely pathogenic ★★ same type
- TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg113Ter Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg323Ter Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg436Ter 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/tbcd-p-ser598 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown