TBCE p.Pro72=
c.216G>C · rs777273223 · VCV2958369
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 -0.26 | GERP -3.4, phastCons 0.003 |
| Overall | ||
| CADD | 0.837 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,862 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.000372%
6/1,613,546 alleles · ultra-rare
exomes 5/1,461,590 · genomes 1/151,956 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,972 |
| European (non-Finnish) | 8.47e-05% | 1,179,976 |
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.Pro72=
- Coding
- c.216G>C
- MANE Select
- NM_003193
- dbSNP
- rs777273223
- Type
- single nucleotide variant
- Location
- chr1:235414463 (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.Pro72Leu Uncertain significance ★★ ⚠ same residue
- TBCE p.Pro72Ser Benign/Likely benign ★★ 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
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-pro72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown