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 -9.2 | GERP -3.2 |
| Overall | ||
| CADD | 0.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 40.9% | 2 |
| European (non-Finnish) | 40.1% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 35.8% | 3 |
| Remaining individualsnot grpmax-eligible | 35.7% | 3 |
| South Asian | 34.6% | 3 |
| Finnishnot grpmax-eligible | 33.2% | 3 |
| African / African-American | 28.3% | 4 |
| Amishnot grpmax-eligible | 27.7% | 4 |
| Admixed American | 24.4% | 4 |
| East Asian | 8.23% | 12 |
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
- VDR
- Protein
- p.Ile352=
- Coding
- c.1056T>C
- MANE Select
- NM_000376
- dbSNP
- rs731236
- Type
- single nucleotide variant
- Location
- chr12:47844974 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 352
- the nr lbd domain; a UniProt-annotated variant site (in vddr2a; loss of calcitriol receptor activity; loss of affinity for calcitriol; no effect on ligand-independent localization to the nucleus); an α-helix
Disease context
vitamin D-dependent rickets, type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: periodontitishepatocellular carcinoma
For Hypocalcemic vitamin D-resistant rickets (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- VDR p.Arg274His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- VDR p.Arg30Ter Pathogenic ★★ same condition
- VDR p.Arg343Cys Likely pathogenic ★★ same condition
- VDR p.Arg391His Pathogenic ★★ same condition
- VDR p.Arg50Ter Pathogenic ★★ same condition
- VDR p.Arg73Gln Pathogenic/Likely pathogenic ★★ same condition
- VDR p.Arg73Ter Pathogenic ★★ same condition
- VDR p.Tyr295Ter Pathogenic ★★ 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/vdr-p-ile352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown