TBCD p.Ser621=
c.1863G>A · rs756930897 · VCV2975547
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00322%, 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 -6.5 | GERP -4.5 |
| Overall | ||
| CADD | 0.505 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00322%
European (non-Finnish) · 38/1,179,558 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00248%
40/1,613,040 alleles · very rare
exomes 38/1,460,792 · genomes 2/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00322% | 31,041 |
| East Asian | 0.00223% | 44,872 |
| Admixed American | 0.00167% | 59,938 |
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.Ser621=
- Coding
- c.1863G>A
- MANE Select
- NM_005993
- dbSNP
- rs756930897
- Type
- single nucleotide variant
- Location
- chr17:82905994 (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-ser621 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown