VDR p.Leu309=
c.927G>C · rs1360270534 · VCV1946890
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000346%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.33 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.94 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 10.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000346%
European (non-Finnish) · 4/1,156,194 alleles
Filtering AF
8.1e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000255%
4/1,567,882 alleles · very rare
exomes 3/1,415,672 · genomes 1/152,210 · 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
- VDR
- Protein
- p.Leu309=
- Coding
- c.927G>C
- MANE Select
- NM_000376
- dbSNP
- rs1360270534
- Type
- single nucleotide variant
- Location
- chr12:47846432 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 309
- 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-leu309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown