TBCD p.Thr994=
c.2982G>A · rs376919689 · VCV1444777
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00988%, sas)
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 -14 | GERP -2.3 |
| Overall | ||
| CADD | 0.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00988%
South Asian · 9/91,076 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00342%
55/1,606,454 alleles · very rare
exomes 49/1,454,100 · genomes 6/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00988% | 10,120 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,611 |
| European (non-Finnish) | 0.00356% | 28,091 |
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.Thr994=
- Coding
- c.2982G>A
- MANE Select
- NM_005993
- dbSNP
- rs376919689
- Type
- single nucleotide variant
- Location
- chr17:82929491 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.45 · 6 PDB
- Residue 994
- a UniProt-annotated variant site (in pebat; uncertain significance)
Similar variants
- TBCD p.Thr994Met 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
- TBCD p.Arg323Ter 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-thr994 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown