Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.97%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.6 | GERP -3.7 |
| Overall | ||
| CADD | 10.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.97%
European (non-Finnish) · 58,652/1,179,478 alleles
Filtering AF
4.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.93%
Overall
4.47%
72,079/1,613,222 alleles · low-frequency
exomes 66,057/1,460,956 · genomes 6,022/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 4.97% | 20 |
| Finnishnot grpmax-eligible | 4.59% | 22 |
| Remaining individualsnot grpmax-eligible | 4.14% | 24 |
| African / African-American | 3.96% | 25 |
| South Asian | 3.2% | 31 |
| Amishnot grpmax-eligible | 3.18% | 31 |
| Admixed American | 2.06% | 49 |
| Ashkenazi Jewishnot grpmax-eligible | 1.73% | 58 |
| Middle Eastern | 1.17% | 85 |
| East Asian | 0.379% | 264 |
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.Ala117=
- Coding
- c.351C>T
- MANE Select
- NM_199334
- dbSNP
- rs2230701
- Type
- single nucleotide variant
- Location
- chr17:40083963 (GRCh38)
- Gene constraint
- LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 10 PDB
- Residue 117
- a DNA-binding region
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.Asp246= Benign/Likely 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-ala117 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown