TSHR p.Lys660Arg
c.1979A>G · VCV3896474
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5575 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5575 | ambiguous |
|---|---|---|
| REVEL | 0.918 | moderately pathogenic-leaning |
| SaProt | LLR -12.11 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 4.9, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 189 kb · p 0.032 · regional, not allelic |
| Overall | ||
| CADD | 25.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TSHR
- Protein
- p.Lys660Arg
- Coding
- c.1979A>G
- MANE Select
- NM_000369
- Type
- single nucleotide variant
- Location
- chr14:81144037 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 9 PDB
- Residue 660
- a UniProt-annotated variant site (in hyperthyroidism; found in hyperfunctioning thyroid adenomas); an α-helix
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-lys660arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown