THRB p.Ser43=
c.129A>T · rs112913751 · VCV754330
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, 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 -5.1 | GERP -5 |
| Overall | ||
| CADD | 2.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,012 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.000929%
15/1,614,108 alleles · ultra-rare
exomes 15/1,461,822 · genomes 0/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,501 |
| European (non-Finnish) | 0.000593% | 168,568 |
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
- THRB
- Protein
- p.Ser43=
- Coding
- c.129A>T
- MANE Select
- NM_001354712
- dbSNP
- rs112913751
- Type
- single nucleotide variant
- Location
- chr3:24190228 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.24 · 34 PDB
- Residue 43
- the 'modulating' region
Similar variants
- PRSS1 p.Ser43= Likely benign ★★ same residue
- PRSS1 p.Asn29Thr Pathogenic ★★ ⚠ same type
- PRSS1 p.Lys23Arg Likely pathogenic ★★ ⚠ same type
- THRB p.Ala268Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
- THRB p.Ala317Thr Pathogenic ★★ ⚠ same type
- THRB p.Arg316His Pathogenic ★★ same type
- THRB p.Arg320Cys Pathogenic ★★ same type
- THRB p.Arg320His Pathogenic/Likely pathogenic ★★ 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/thrb-p-ser43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown