TBCE p.His49=
c.147T>C · rs764497359 · VCV2955084
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, afr)
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 -2.4 | GERP 1.4 |
| Overall | ||
| CADD | 6.866 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
African / African-American · 13/74,920 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00813%
Overall
0.000929%
15/1,613,868 alleles · ultra-rare
exomes 9/1,461,696 · genomes 6/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0174% | 5,763 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,797 |
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.His49=
- Coding
- c.147T>C
- MANE Select
- NM_003193
- dbSNP
- rs764497359
- Type
- single nucleotide variant
- Location
- chr1:235401549 (GRCh38)
- Gene constraint
- LOEUF 0.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.27 · 6 PDB
- Residue 49
- the cap-gly domain
Similar variants
- TBCE p.His49Pro 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-his49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown