RORA p.Thr468=
c.1404A>G · VCV4822044
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.185%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -6.6 |
| Overall | ||
| CADD | 3.543 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.185%
South Asian · 167/90,102 alleles
Filtering AF
0.162%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.154%
Overall
0.0112%
177/1,581,410 alleles · rare
exomes 171/1,429,140 · genomes 6/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.185% | 540 |
| Middle Eastern | 0.0168% | 5,970 |
| Remaining individualsnot grpmax-eligible | 0.00979% | 10,213 |
| African / African-American | 0.0027% | 37,010 |
| European (non-Finnish) | 8.68e-05% | 1,152,542 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- RORA
- Protein
- p.Thr468=
- Coding
- c.1404A>G
- MANE Select
- NM_134261
- Type
- single nucleotide variant
- Location
- chr15:60499895 (GRCh38)
- Gene constraint
- LOEUF 0.207 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.40 · 3 PDB
- Residue 468
- the nr lbd domain; an α-helix
Similar variants
- RORA p.Arg462Ter Pathogenic/Likely pathogenic ★★ same type
- RORA p.Arg500Ter Pathogenic/Likely pathogenic ★★ same type
- RORA p.Ala11Val Uncertain significance ★★ ⚠ same type
- RORA p.Ala358Thr Uncertain significance ★★ same type
- RORA p.Ala7Ser Uncertain significance ★★ ⚠ same type
- RORA p.Arg170His Uncertain significance ★★ ⚠ same type
- RORA p.Arg462Gln Uncertain significance ★★ ⚠ same type
- RORA p.Arg47Thr Uncertain significance ★★ 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-thr468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown