RORA p.Arg500Ter
c.1498C>T · rs1555421544 · VCV559568
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
RORA-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 5, phastCons 1 |
| Overall | ||
| CADD | 42.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- RORA
- Protein
- p.Arg500Ter
- Coding
- c.1498C>T
- MANE Select
- NM_134261
- dbSNP
- rs1555421544
- Type
- single nucleotide variant
- Location
- chr15:60497529 (GRCh38)
- Gene constraint
- LOEUF 0.207 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.40 · 3 PDB
- Residue 500
- the nr lbd domain; a UniProt-annotated variant site (in iddeca; uncertain significance); an α-helix
Disease context
RORA-related disorder
Similar variants
- RORA p.Arg140Ter Likely pathogenic ★ same condition
- RORA c.1076-6G>A Uncertain significance ★ same condition
- RORA c.197-26463C>G Uncertain significance same condition
- RORA p.His275Tyr Uncertain significance ⚠ same condition
- RORA p.Ala338= Likely benign same condition
- RORA p.Leu156= Likely benign same condition
- RORA p.Arg340fs Pathogenic/Likely pathogenic same condition
- RORA p.Arg462Ter 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/rora-p-arg500ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown