Is VDR p.Cys84fs (c.249del) pathogenic?

VDR p.Cys84fs (c.249del) is classified Pathogenic in VDR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-20). Absent from gnomAD.

How common is VDR p.Cys84fs (c.249del) in the general population?

VDR p.Cys84fs (c.249del) is absent from gnomAD (gnomAD).

VDR p.Cys84fs

c.249del · rs2539996264 · VCV2839317

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: VDR
Protein: p.Cys84fs
Coding: c.249del
MANE Select: NM_000376
dbSNP: rs2539996264
Type: Deletion
Location: chr12:47865075 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB
Residue 84: a DNA-binding region; an α-helix

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

Similar variants

VDR p.Cys84= Likely benign ★ same residue
VDR p.Asn394_Ter428delinsXaa Pathogenic ★ same type
VDR p.Leu313fs Likely pathogenic ★ same type
VDR c.*2118_*2122del Uncertain significance ★ same type
VDR p.Thr415fs Uncertain significance ★ same type
VDR c.1025-24_1025-19del Likely benign ★ same type
VDR c.147-22_147-12del Likely benign ★ same type
VDR c.277+11del Likely benign ★ 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-cys84fs (accessed [today's date]).

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