TBCE p.Arg135=
c.403A>C · rs141117231 · VCV743230
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0748%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 11.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0748%
African / African-American · 56/74,872 alleles
Filtering AF
0.0591%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0534%
Overall
0.0044%
71/1,613,980 alleles · ultra-rare
exomes 36/1,461,886 · genomes 35/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0748% | 1,337 |
| Admixed American | 0.0133% | 7,500 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| European (non-Finnish) | 0.000254% | 393,340 |
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
- TBCE
- Protein
- p.Arg135=
- Coding
- c.403A>C
- MANE Select
- NM_003193
- dbSNP
- rs141117231
- Type
- single nucleotide variant
- Location
- chr1:235419504 (GRCh38)
- Gene constraint
- LOEUF 0.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.27 · 6 PDB
Similar variants
- TBCE c.100+1G>A Pathogenic/Likely pathogenic ★★ same type
- TBCE p.Arg12Ter Likely pathogenic ★★ same type
- TBCE p.Gln123Ter Pathogenic/Likely pathogenic ★★ same type
- TBCE p.Ile155Asn Pathogenic/Likely pathogenic ★★ same type
- TBCE p.Lys145Ter Pathogenic/Likely pathogenic ★★ same type
- B3GALNT2 p.Gly492Ser Uncertain significance ★★ ⚠ same type
- TBCE c.738-3C>T Uncertain significance ★★ same type
- TBCE c.898+5A>G Uncertain significance ★★ 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/tbce-p-arg135 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown