TBCD p.Ala493=
c.1479A>C · rs112420156 · VCV1250592
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 8.06%, afr) — too common for a highly-penetrant pathogenic allele
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 -11 | GERP -4.7 |
| Overall | ||
| CADD | 0.055 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.06%
African / African-American · 6,039/74,948 alleles
Filtering AF
7.89%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.82%
Overall
2.15%
34,631/1,608,724 alleles · common
exomes 29,519/1,456,456 · genomes 5,112/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.06% | 12 |
| Amishnot grpmax-eligible | 2.52% | 40 |
| European (non-Finnish) | 2.1% | 48 |
| Remaining individualsnot grpmax-eligible | 1.95% | 51 |
| South Asian | 1.55% | 64 |
| Middle Eastern | 1.01% | 99 |
| Admixed American | 0.948% | 105 |
| Ashkenazi Jewishnot grpmax-eligible | 0.685% | 146 |
| Finnishnot grpmax-eligible | 0.617% | 162 |
| East Asian | 0.00223% | 44,788 |
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.Ala493=
- Coding
- c.1479A>C
- MANE Select
- NM_005993
- dbSNP
- rs112420156
- Type
- single nucleotide variant
- Location
- chr17:82884148 (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-ala493 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown