Is VDR c.*2900A>C pathogenic?

VDR c.2900A>C is classified Uncertain significance in VDR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Low-frequency (popmax 1.45%, sas); Associated with vitamin D-dependent rickets, type 2A.

What condition is associated with VDR c.*2900A>C?

VDR c.*2900A>C is associated with vitamin D-dependent rickets, type 2A (ClinVar).

How common is VDR c.*2900A>C in the general population?

VDR c.*2900A>C is low-frequency (popmax 1.45%, sas) (gnomAD).

How is Hypocalcemic vitamin D-resistant rickets inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

VDR c.*2900A>C

rs527373238 · VCV308813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.45%, sas)

Conditions

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 0.33	GERP 1.1
Non-coding constraint	Z 0.06	1 kb window · o/e 1.00 · regional · uncalibrated
Overall
CADD	2.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.45% South Asian · 70/4,818 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.0466% 71/152,334 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.45%	69
African / African-American	0.00241%	41,578

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
Coding: c.*2900A>C
MANE Select: NM_000376
dbSNP: rs527373238
Type: single nucleotide variant
Location: chr12:47841846 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB

Full VDR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

vitamin D-dependent rickets, type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypocalcemic vitamin D-resistant rickets (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
VDR p.Arg73Ter Pathogenic ★★ same condition
VDR p.Tyr295Ter 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-c-star-2900a-c (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown