VDR p.Ser278=
c.834C>T · rs2539969299 · VCV2729689
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 0.6 | GERP 0.68, phastCons 0.99 |
| Overall | ||
| CADD | 8.682 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- VDR
- Protein
- p.Ser278=
- Coding
- c.834C>T
- MANE Select
- NM_000376
- dbSNP
- rs2539969299
- Type
- single nucleotide variant
- Location
- chr12:47846730 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 278
- the nr lbd domain; a binding site; 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)
Similar variants
- VDR p.Ser278fs Pathogenic/Likely pathogenic ★★ same residue
- 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
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-ser278 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown