THRB p.Leu290=
c.870G>A · VCV4532950
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.152%, sas)
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 6 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 11.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.152%
South Asian · 138/91,074 alleles
Filtering AF
0.131%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.00892%
144/1,614,110 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.152% | 660 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.Leu290=
- Coding
- c.870G>A
- MANE Select
- NM_001354712
- Type
- single nucleotide variant
- Location
- chr3:24133331 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.24 · 34 PDB
- Residue 290
- the nr lbd domain; the 'interaction with nr2f6' region
Similar variants
- 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
- THRB p.Arg338Trp 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-leu290 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown