TSHR p.Asp86=
c.258T>C · rs769501905 · VCV2976146
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, afr)
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 -2.6 | GERP -3.8 |
| Overall | ||
| CADD | 2.017 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
African / African-American · 16/74,872 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.0013%
21/1,613,034 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0214% | 4,680 |
| Admixed American | 0.005% | 19,992 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,438 |
| European (non-Finnish) | 8.48e-05% | 1,179,372 |
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.Asp86=
- Coding
- c.258T>C
- MANE Select
- NM_000369
- dbSNP
- rs769501905
- Type
- single nucleotide variant
- Location
- chr14:81068269 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 9 PDB
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-asp86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown