VDR p.Ser199=
c.597G>A · rs565845200 · VCV1939688
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
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 -10 | GERP -3.1 |
| Overall | ||
| CADD | 0.462 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,072 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.0013%
21/1,613,950 alleles · very rare
exomes 17/1,461,672 · genomes 4/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,384 |
| African / African-American | 0.00533% | 18,753 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| European (non-Finnish) | 0.000508% | 196,664 |
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.Ser199=
- Coding
- c.597G>A
- MANE Select
- NM_000376
- dbSNP
- rs565845200
- Type
- single nucleotide variant
- Location
- chr12:47855788 (GRCh38)
- Gene constraint
- LOEUF 0.714 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.56 · 52 PDB
- Residue 199
- 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)
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-ser199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown