THRB p.Arg320Pro
c.959G>C · VCV4682108
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9993 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
hyperthyroidism
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9993 | likely pathogenic ✓ concordant with ClinVar · top 8% in THRB |
|---|---|---|
| REVEL | 0.961 | strongly pathogenic-leaning |
| SaProt | LLR -18.80 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.29 | constrained · MANE · 10 kb · p 5.8e-19 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | 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
- THRB
- Protein
- p.Arg320Pro
- Coding
- c.959G>C
- MANE Select
- NM_001354712
- Type
- single nucleotide variant
- Location
- chr3:24127684 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.24 · 34 PDB
- Residue 320
- the nr lbd domain; a UniProt-annotated variant site (in grthd); the 'interaction with nr2f6' region
Similar variants
- THRB p.Arg320His Pathogenic/Likely pathogenic ★★ same residue
- THRB p.Arg320Cys Pathogenic ★★ same residue
- THRB p.Arg320Ser Uncertain significance ★★ ⚠ same residue
- THRB p.Arg320Leu Pathogenic same residue
- THRB p.Ala317Thr Pathogenic ★★ ⚠ same condition
- THRB p.Arg429Gln Pathogenic/Likely pathogenic ★★ same condition
- THRB p.Arg438His Pathogenic ★★ ⚠ same condition
- THRB p.His435Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
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/thrb-p-arg320pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown