RORA p.Ser216=
c.648C>T · rs148197507 · VCV770623
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
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 -1.9 | GERP -12 |
| Overall | ||
| CADD | 6.199 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,062 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0294%
Overall
0.022%
355/1,614,182 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| Admixed American | 0.0333% | 3,001 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| South Asian | 0.0253% | 3,960 |
| European (non-Finnish) | 0.0236% | 4,245 |
| African / African-American | 0.016% | 6,251 |
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.Ser216=
- Coding
- c.648C>T
- MANE Select
- NM_134261
- dbSNP
- rs148197507
- Type
- single nucleotide variant
- Location
- chr15:60511398 (GRCh38)
- Gene constraint
- LOEUF 0.207 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.40 · 3 PDB
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-ser216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown