RORA p.Arg462Ter
c.1384C>T · rs1198203108 · VCV1691814
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Inborn genetic diseases
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 within the last 50 nt of the penultimate exon (10 of 11, 23 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 5, phastCons 1 |
| Overall | ||
| CADD | 44.0 | 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.Arg462Ter
- Coding
- c.1384C>T
- MANE Select
- NM_134261
- dbSNP
- rs1198203108
- Type
- single nucleotide variant
- Location
- chr15:60499915 (GRCh38)
- Gene constraint
- LOEUF 0.207 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.40 · 3 PDB
- Residue 462
- the nr lbd domain; a UniProt-annotated variant site (in iddeca; loss of function in cerebellar development, when assayed in a heterologous system)
Similar variants
- RORA p.Arg462Gln Uncertain significance ★★ ⚠ same residue
- RORA p.Ala7Ser Uncertain significance ★★ ⚠ same condition
- RORA p.Gln278His Uncertain significance ★★ ⚠ same condition
- RORA p.Gly211Arg Uncertain significance ★★ ⚠ same condition
- RORA p.Lys151Gln Uncertain significance ★★ ⚠ same condition
- RORA p.Thr328Arg Uncertain significance ★★ ⚠ same condition
- RORA c.197-26379G>A Likely benign ★★ same condition
- RORA p.Asp21Gly Likely benign ★★ 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/rora-p-arg462ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown