Is VDR p.Arg30Ter (c.88C>T) pathogenic?

VDR p.Arg30Ter (c.88C>T) is classified Pathogenic in VDR (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-01-04). Very rare (popmax 0.00669%, eas); Associated with VDR-related disorder.

What condition is associated with VDR p.Arg30Ter (c.88C>T)?

VDR p.Arg30Ter (c.88C>T) is associated with VDR-related disorder, vitamin D-dependent rickets, type 2A (ClinVar).

How common is VDR p.Arg30Ter (c.88C>T) in the general population?

VDR p.Arg30Ter (c.88C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

VDR p.Arg30Ter

c.88C>T · rs121909801 · VCV7757

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

VDR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.72, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00186% 30/1,613,814 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
Remaining individualsnot grpmax-eligible	0.0032%	31,230
South Asian	0.0022%	45,546
European (non-Finnish)	0.00195%	51,305

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.Arg30Ter
Coding: c.88C>T
MANE Select: NM_000376
dbSNP: rs121909801
Type: single nucleotide variant
Location: chr12:47879026 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB
Residue 30: a DNA-binding region

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

Disease context

VDR-related disorder

Also linked: vitamin D-dependent rickets, type 2A

Similar variants

VDR p.Arg30Gln Uncertain significance ★★ same residue
VDR p.Arg274His Pathogenic/Likely 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-p-arg30ter (accessed [today's date]).

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