RORC p.Ile46=
c.138C>T · VCV4911079
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, sas)
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 2.5 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 9.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
South Asian · 28/91,086 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.0018%
29/1,613,952 alleles · ultra-rare
exomes 29/1,461,654 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0307% | 3,253 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
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
- RORC
- Protein
- p.Ile46=
- Coding
- c.138C>T
- MANE Select
- NM_005060
- Type
- single nucleotide variant
- Location
- chr1:151817213 (GRCh38)
- Gene constraint
- LOEUF 0.351 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.42 · 162 PDB
- Residue 46
- a DNA-binding region
Similar variants
- RORC p.Arg10Gln Uncertain significance ★★ ⚠ same type
- RORC p.Arg13Trp Uncertain significance ★★ ⚠ same type
- RORC p.Arg208Gln Uncertain significance ★★ ⚠ same type
- RORC p.Arg237Ser Uncertain significance ★★ ⚠ same type
- RORC p.Arg257His Uncertain significance ★★ ⚠ same type
- RORC p.Arg288Gln Uncertain significance ★★ ⚠ same type
- RORC p.Arg82Gln Uncertain significance ★★ ⚠ same type
- RORC p.Asn373Ser 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/rorc-p-ile46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown