THRA p.Asp246=
c.738C>T · rs41283431 · VCV259021
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.39%, mid)
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 4.9 | GERP 0.79, phastCons 1 |
| Overall | ||
| CADD | 13.35 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.39%
Middle Eastern · 83/5,974 alleles
Filtering AF
1.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.06%
Overall
0.42%
6,689/1,593,706 alleles · low-frequency
exomes 6,203/1,441,368 · genomes 486/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.39% | 72 |
| Finnishnot grpmax-eligible | 0.718% | 139 |
| European (non-Finnish) | 0.483% | 207 |
| Remaining individualsnot grpmax-eligible | 0.406% | 247 |
| Admixed American | 0.272% | 368 |
| Ashkenazi Jewishnot grpmax-eligible | 0.114% | 875 |
| African / African-American | 0.0575% | 1,739 |
| South Asian | 0.033% | 3,031 |
| East Asian | 0.00224% | 44,658 |
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.Asp246=
- Coding
- c.738C>T
- MANE Select
- NM_199334
- dbSNP
- rs41283431
- Type
- single nucleotide variant
- Location
- chr17:40088256 (GRCh38)
- Gene constraint
- LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 10 PDB
- Residue 246
- the nr lbd domain; an α-helix
Similar variants
- 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.Asp50= Likely benign ★★ same type
- THRA p.Glu285= 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-asp246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown