Is DLL3 p.Val183fs (c.546_547del) pathogenic?

DLL3 p.Val183fs (c.546547del) is classified Likely pathogenic in DLL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Associated with spondylocostal dysostosis 1, autosomal recessive.

What condition is associated with DLL3 p.Val183fs (c.546_547del)?

DLL3 p.Val183fs (c.546_547del) is associated with spondylocostal dysostosis 1, autosomal recessive (ClinVar).

DLL3 p.Val183fs

c.546_547del · VCV3583896

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spondylocostal dysostosis 1, autosomal recessive

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 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 1

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

Variant & gene context

Gene: DLL3
Protein: p.Val183fs
Coding: c.546_547del
MANE Select: NM_203486
Type: Deletion
Location: chr19:39502951 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42
Residue 183: the dsl domain

Full DLL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondylocostal dysostosis 1, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL3 p.Ala317fs Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Cys207fs Pathogenic ★★ same condition
DLL3 p.Gly132fs Pathogenic ★★ same condition
DLL3 p.Ile123fs Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Ala81fs Likely pathogenic ★ same condition
DLL3 p.Pro43fs Likely pathogenic ★ same condition
DLL3 p.Pro481fs Likely pathogenic ★ same condition
DLL3 p.Val183= Likely benign ★ same residue

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/dll3-p-val183fs (accessed [today's date]).

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