VDR p.Leu313fs
c.937del · VCV3574599
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
vitamin D-dependent rickets, type 2A
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 9 of 10 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- VDR
- Protein
- p.Leu313fs
- Coding
- c.937del
- MANE Select
- NM_000376
- Type
- Deletion
- Location
- chr12:47846422 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 313
- 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 & treatmentsFor Hypocalcemic vitamin D-resistant rickets (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- VDR p.Thr415fs Uncertain significance ★ same condition
- VDR p.Lys123fs Pathogenic same condition
- 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
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-leu313fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown