TSHB p.Pro93=
c.279C>T · rs1010297279 · VCV2799340
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.6 | GERP -4.8, phastCons 0.04 |
| Overall | ||
| CADD | 5.159 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,988 alleles
Overall
6.2e-05%
1/1,613,788 alleles · very rare
exomes 1/1,461,612 · genomes 0/152,176 · joint denominator
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
- TSHB
- Protein
- p.Pro93=
- Coding
- c.279C>T
- MANE Select
- NM_000549
- dbSNP
- rs1010297279
- Type
- single nucleotide variant
- Location
- chr1:115034089 (GRCh38)
- Gene constraint
- LOEUF 1.532 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.28 · 3 PDB
- Residue 93
- a UniProt-annotated variant site (in chng4)
Similar variants
- TSHB c.162+5G>A Pathogenic ★★ same type
- TSHB p.Gln69Ter Pathogenic/Likely pathogenic ★★ same type
- TSHB p.Gly49Arg Pathogenic/Likely pathogenic ★★ same type
- TSHB p.Ala100Thr Uncertain significance ★★ ⚠ same type
- TSHB p.Gly86Arg Uncertain significance ★★ ⚠ same type
- TSHB c.162+16C>T Benign/Likely benign ★★ same type
- TSHB c.163-4C>G Likely benign ★★ same type
- TSHB p.Ala18= Likely benign ★★ 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/tshb-p-pro93 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown