THRA p.Pro398Arg
c.1193C>G · rs876657396 · VCV192273
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Paediatric disorders
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.963 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.25 | constrained · MANE · 118 bp · p 1.7e-08 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
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
- THRA
- Protein
- p.Pro398Arg
- Coding
- c.1193C>G
- MANE Select
- NM_199334
- dbSNP
- rs876657396
- Type
- single nucleotide variant
- Location
- chr17:40089416 (GRCh38)
- Gene constraint
- LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 10 PDB
- Residue 398
- the nr lbd domain; a UniProt-annotated variant site (in chng6)
Similar variants
- THRA p.Ala263Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- THRA p.Glu403Lys Pathogenic/Likely pathogenic ★★ same condition
- THRA p.Gly291Ser Pathogenic/Likely pathogenic ★★ same condition
- THRA p.Glu173Gly Likely pathogenic ★ same condition
- THRA p.His381Tyr Likely pathogenic ★ same condition
- THRA p.Ile299Thr Likely pathogenic ★ ⚠ same condition
- THRA p.Leu274Arg Likely pathogenic ★ same condition
- THRA p.Thr273Asn 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/thra-p-pro398arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown