Is VDR p.Ser278fs (c.832_833insA) pathogenic?

VDR p.Ser278fs (c.832833insA) is classified Pathogenic/Likely pathogenic in VDR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-24). Absent from gnomAD; Associated with VDR-related disorder.

What condition is associated with VDR p.Ser278fs (c.832_833insA)?

VDR p.Ser278fs (c.832_833insA) is associated with VDR-related disorder (ClinVar).

How common is VDR p.Ser278fs (c.832_833insA) in the general population?

VDR p.Ser278fs (c.832_833insA) is absent from gnomAD (gnomAD).

VDR p.Ser278fs

c.832_833insA · rs1945288336 · VCV944287

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

VDR-related disorder

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 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, 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.Ser278fs
Coding: c.832_833insA
MANE Select: NM_000376
dbSNP: rs1945288336
Type: Insertion
Location: chr12:47846731 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB
Residue 278: the nr lbd domain; a binding site; 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)

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

Disease context

VDR-related disorder

Similar variants

VDR p.Ser278= Likely benign ★ same residue
VDR p.Arg30Ter Pathogenic ★★ same condition
VDR p.Tyr295Ter Pathogenic ★★ same condition
VDR p.Val346Met Pathogenic/Likely pathogenic ★★ same condition
VDR p.Val261Ile Uncertain significance ★★ ⚠ same condition
VDR c.584-2A>G Likely pathogenic ★ same condition
VDR p.Asp17His Uncertain significance ★ ⚠ same condition
VDR p.Arg18Gln Uncertain significance ⚠ 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-ser278fs (accessed [today's date]).

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