RORA p.Phe399=
c.1197T>C · VCV4925279
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0012%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 7.906 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0012%
European (non-Finnish) · 14/1,166,938 alleles
Filtering AF
0.000696%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000545%
Overall
0.000876%
14/1,598,378 alleles · very rare
exomes 14/1,446,128 · genomes 0/152,250 · joint denominator
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.Phe399=
- Coding
- c.1197T>C
- MANE Select
- NM_134261
- Type
- single nucleotide variant
- Location
- chr15:60501056 (GRCh38)
- Gene constraint
- LOEUF 0.207 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.40 · 3 PDB
- Residue 399
- 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-phe399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown