TBCD p.Pro1122=
c.3366G>A · rs375632401 · VCV1539096
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, 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 -10 | GERP -3 |
| Overall | ||
| CADD | 0.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
European (non-Finnish) · 177/1,179,720 alleles
Filtering AF
0.0132%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.0125%
201/1,611,508 alleles · ultra-rare
exomes 178/1,459,278 · genomes 23/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.015% | 6,665 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,922 |
| Finnishnot grpmax-eligible | 0.0142% | 7,062 |
| South Asian | 0.0033% | 30,283 |
| African / African-American | 0.00267% | 37,438 |
| Admixed American | 0.00167% | 59,942 |
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.Pro1122=
- Coding
- c.3366G>A
- MANE Select
- NM_005993
- dbSNP
- rs375632401
- Type
- single nucleotide variant
- Location
- chr17:82938133 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.45 · 6 PDB
- Residue 1122
- a UniProt-annotated variant site (in pebat; severely decreased protein abundance; does not affect localization to centrosome; decreased interaction with arl2; decreased interaction with tbce; decreased interaction with beta tubulin)
Similar variants
- TBCD p.Pro1122Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro1122 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown