TBCD p.Ala477=
c.1431C>A · rs373903003 · VCV1575608
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0182%, 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 3.2 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 8.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0182%
European (non-Finnish) · 215/1,179,874 alleles
Filtering AF
0.0162%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0154%
Overall
0.0142%
229/1,613,378 alleles · ultra-rare
exomes 212/1,461,134 · genomes 17/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0182% | 5,488 |
| African / African-American | 0.0107% | 9,370 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,492 |
| Admixed American | 0.00167% | 60,000 |
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.Ala477=
- Coding
- c.1431C>A
- MANE Select
- NM_005993
- dbSNP
- rs373903003
- Type
- single nucleotide variant
- Location
- chr17:82870336 (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-ala477 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown