Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.582%, eas)
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. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP 0.48, phastCons 0.98 |
| Overall | ||
| CADD | 7.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.582%
East Asian · 261/44,880 alleles
Filtering AF
0.524%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.501%
Overall
0.0279%
450/1,614,218 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.582% | 172 |
| South Asian | 0.182% | 549 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00167% | 60,028 |
| African / African-American | 0.00133% | 75,070 |
| European (non-Finnish) | 0.000339% | 295,005 |
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.Arg402=
- Coding
- c.1206C>A
- MANE Select
- NM_000376
- dbSNP
- rs2229829
- Type
- single nucleotide variant
- Location
- chr12:47844824 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 402
- 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.Arg402Cys Uncertain significance ★ ⚠ same residue
- VDR p.Arg402His Uncertain significance ★ ⚠ same residue
- 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-arg402 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown