VDR p.Leu332=
c.994C>T · rs1310783575 · VCV1672922
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00226%, eas)
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 5 | GERP 0.87, phastCons 1 |
| Overall | ||
| CADD | 10.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00226%
East Asian · 1/44,276 alleles
Overall
0.000138%
2/1,451,548 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00226% | 44,276 |
| European (non-Finnish) | 8.51e-05% | 1,175,758 |
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.Leu332=
- Coding
- c.994C>T
- MANE Select
- NM_000376
- dbSNP
- rs1310783575
- Type
- single nucleotide variant
- Location
- chr12:47846365 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 332
- 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
Similar variants
- VDR p.Arg274His Pathogenic/Likely pathogenic ★★ ⚠ same type
- VDR p.Arg30Ter Pathogenic ★★ same type
- VDR p.Arg343Cys Likely pathogenic ★★ same type
- VDR p.Arg391His Pathogenic ★★ same type
- VDR p.Arg50Ter Pathogenic ★★ same type
- VDR p.Arg73Gln Pathogenic/Likely pathogenic ★★ same type
- VDR p.Arg73Ter Pathogenic ★★ same type
- VDR p.Tyr295Ter Pathogenic ★★ 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/vdr-p-leu332 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown