TBCD p.Leu437=
c.1311C>T · rs371961650 · VCV2080785
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0715%, eas)
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 -1.3 | GERP -3 |
| Overall | ||
| CADD | 1.647 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0715%
East Asian · 32/44,778 alleles
Filtering AF
0.052%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0453%
Overall
0.00546%
88/1,611,888 alleles · ultra-rare
exomes 79/1,459,674 · genomes 9/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0715% | 1,399 |
| Middle Eastern | 0.0331% | 3,023 |
| South Asian | 0.0165% | 6,050 |
| African / African-American | 0.008% | 12,493 |
| Admixed American | 0.00668% | 14,960 |
| European (non-Finnish) | 0.00246% | 40,665 |
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.Leu437=
- Coding
- c.1311C>T
- MANE Select
- NM_005993
- dbSNP
- rs371961650
- Type
- single nucleotide variant
- Location
- chr17:82814927 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.45 · 6 PDB
Similar variants
- ZNF750 p.Ala437Thr Uncertain significance ★ ⚠ same residue
- ZNF750 p.Ala437Val Uncertain significance ★ ⚠ same residue
- 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
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-leu437 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown