Is VDR p.Arg54= (c.162G>A) pathogenic?

VDR p.Arg54= (c.162G>A) is classified Likely benign in VDR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0164%, mid); Associated with vitamin D-dependent rickets, type 2A.

What condition is associated with VDR p.Arg54= (c.162G>A)?

VDR p.Arg54= (c.162G>A) is associated with vitamin D-dependent rickets, type 2A (ClinVar).

How common is VDR p.Arg54= (c.162G>A) in the general population?

VDR p.Arg54= (c.162G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Hypocalcemic vitamin D-resistant rickets inherited?

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

VDR p.Arg54=

c.162G>A · rs774173372 · VCV1640006

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 0.15	GERP 0.78, phastCons 0.95
Overall
CADD	9.378	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00384% 62/1,612,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.00833%	12,000
Remaining individualsnot grpmax-eligible	0.00641%	15,608
European (non-Finnish)	0.00424%	23,586
Finnishnot grpmax-eligible	0.00158%	63,478
South Asian	0.0011%	91,076

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.Arg54=
Coding: c.162G>A
MANE Select: NM_000376
dbSNP: rs774173372
Type: single nucleotide variant
Location: chr12:47865162 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB
Residue 54: a DNA-binding region

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.Arg54Gln Uncertain significance ★★ ⚠ same residue
VDR p.Arg54Trp 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-arg54 (accessed [today's date]).

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