THRA p.Arg284=
c.850C>A · rs772512292 · VCV724667
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00898%, 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 2.7 | GERP 0.74, phastCons 1 |
| Overall | ||
| CADD | 12.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00898%
European (non-Finnish) · 106/1,179,994 alleles
Filtering AF
0.00757%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00706%
Overall
0.00669%
108/1,613,992 alleles · very rare
exomes 104/1,461,814 · genomes 4/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00898% | 11,132 |
| African / African-American | 0.00267% | 37,462 |
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.Arg284=
- Coding
- c.850C>A
- MANE Select
- NM_199334
- dbSNP
- rs772512292
- Type
- single nucleotide variant
- Location
- chr17:40088368 (GRCh38)
- Gene constraint
- LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 10 PDB
- Residue 284
- the nr lbd domain; an α-helix
Similar variants
- THRA p.Arg284Pro Uncertain significance ★ ⚠ same residue
- THRA p.Arg284Trp 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
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-arg284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown