TSHR p.Asp232=
c.696C>T · rs750560312 · VCV753645
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0367%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.8 |
| Overall | ||
| CADD | 0.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0367%
Admixed American · 22/60,000 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.00564%
91/1,613,964 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0367% | 2,727 |
| Middle Eastern | 0.0333% | 2,999 |
| South Asian | 0.00878% | 11,384 |
| European (non-Finnish) | 0.00466% | 21,455 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,235 |
| Finnishnot grpmax-eligible | 0.00312% | 32,022 |
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
- TSHR
- Protein
- p.Asp232=
- Coding
- c.696C>T
- MANE Select
- NM_000369
- dbSNP
- rs750560312
- Type
- single nucleotide variant
- Location
- chr14:81139682 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 9 PDB
- Residue 232
- a β-strand
Similar variants
- TSHR c.881+1G>A Pathogenic/Likely pathogenic ★★ same type
- TSHR c.881+1G>T Pathogenic/Likely pathogenic ★★ same type
- TSHR p.Ala553Thr Pathogenic/Likely pathogenic ★★ same type
- TSHR p.Arg109Gln Pathogenic/Likely pathogenic ★★ same type
- TSHR p.Arg450His Pathogenic/Likely pathogenic ★★ same type
- TSHR p.Arg519Cys Pathogenic ★★ same type
- TSHR p.Arg519His Pathogenic/Likely pathogenic ★★ same type
- TSHR p.Cys390Trp Pathogenic/Likely pathogenic ★★ ⚠ 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/tshr-p-asp232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown