TBCE p.Pro295=
c.885G>A · rs768389458 · VCV2142357
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.32 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.28 | loss · gain 0.05 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -2.5 |
| Overall | ||
| CADD | 6.547 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00112%
18/1,613,896 alleles · ultra-rare
exomes 17/1,461,774 · genomes 1/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| South Asian | 0.00769% | 13,009 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,256 |
| European (non-Finnish) | 0.000678% | 147,490 |
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.Pro295=
- Coding
- c.885G>A
- MANE Select
- NM_003193
- dbSNP
- rs768389458
- Type
- single nucleotide variant
- Location
- chr1:235436437 (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 p.Pro295Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro295 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown