THRB p.Val349=
c.1047G>A · rs745984020 · VCV3054053
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Conditions
1
THRB-related disorder
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 0.26 | GERP -1, phastCons 0.98 |
| Overall | ||
| CADD | 7.847 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,002 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00217%
35/1,614,078 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,616 |
| European (non-Finnish) | 0.00186% | 53,638 |
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.Val349=
- Coding
- c.1047G>A
- MANE Select
- NM_001354712
- dbSNP
- rs745984020
- Type
- single nucleotide variant
- Location
- chr3:24127596 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.24 · 34 PDB
- Residue 349
- the nr lbd domain; the 'interaction with nr2f6' region; an α-helix
Disease context
THRB-related disorder
Similar variants
- THRB p.Val349Met Likely pathogenic ★★ ⚠ same residue
- THRB p.Val349Glu Likely pathogenic same residue
- THRB p.Arg316His Pathogenic ★★ same condition
- THRB p.Arg383His Pathogenic/Likely pathogenic ★★ same condition
- THRB p.Arg438Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- THRB p.Gly332Glu Likely pathogenic ★★ same condition
- THRB p.His435Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- THRB p.Ile250Thr Likely pathogenic ★★ ⚠ same condition
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-val349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown