THRB p.Pro247=
c.741A>G · VCV3895575
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor loss, 2 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.8 | GERP -4.1 |
| Overall | ||
| CADD | 1.211 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,179,968 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,090 alleles · very rare
exomes 2/1,461,786 · genomes 0/152,304 · 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
- THRB
- Protein
- p.Pro247=
- Coding
- c.741A>G
- MANE Select
- NM_001354712
- Type
- single nucleotide variant
- Location
- chr3:24133460 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.24 · 34 PDB
- Residue 247
- the nr lbd domain; the 'interaction with nr2f6' region
Similar variants
- THRB p.Pro247Leu Likely pathogenic ★ ⚠ same residue
- PRSS1 p.Ser247Gly Uncertain significance ★ ⚠ same residue
- PRSS1 p.Ser247Ile Uncertain significance ★ 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
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-pro247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown