THRA p.Lys147=
c.441G>A · rs1367628384 · VCV739650
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000678%, nfe)
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 3.4 | GERP -0.35, phastCons 1 |
| Overall | ||
| CADD | 9.538 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000678%
European (non-Finnish) · 8/1,180,000 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000547%
8/1,461,826 alleles · very rare
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
- THRA
- Protein
- p.Lys147=
- Coding
- c.441G>A
- MANE Select
- NM_199334
- dbSNP
- rs1367628384
- Type
- single nucleotide variant
- Location
- chr17:40084680 (GRCh38)
- Gene constraint
- LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 10 PDB
Similar variants
- THRA p.Lys147del Uncertain significance ★ same residue
- THRA p.Ala263Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- THRA p.Glu403Lys Pathogenic/Likely pathogenic ★★ same type
- THRA p.Gly291Ser Pathogenic/Likely pathogenic ★★ same type
- THRA p.Met238Thr Uncertain significance ★★ ⚠ same type
- THRA c.223-5C>G Benign/Likely benign ★★ same type
- THRA p.Ala117= Benign ★★ same type
- THRA p.Asp246= Benign/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/thra-p-lys147 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown