Is DLL3 p.His447fs (c.1339_1340insT) pathogenic?

DLL3 p.His447fs (c.13391340insT) is classified Pathogenic in DLL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Absent from gnomAD; Associated with spondylocostal dysostosis 1, autosomal recessive.

What condition is associated with DLL3 p.His447fs (c.1339_1340insT)?

DLL3 p.His447fs (c.1339_1340insT) is associated with spondylocostal dysostosis 1, autosomal recessive (ClinVar).

How common is DLL3 p.His447fs (c.1339_1340insT) in the general population?

DLL3 p.His447fs (c.1339_1340insT) is absent from gnomAD (gnomAD).

DLL3 p.His447fs

c.1339_1340insT · rs2514649158 · VCV1705307

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

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP -3.3, 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: DLL3
Protein: p.His447fs
Coding: c.1339_1340insT
MANE Select: NM_203486
dbSNP: rs2514649158
Type: Insertion
Location: chr19:39507284 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42
Residue 447: the egf-like 6 domain; a disulfide bond

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 c.652+1G>T Likely pathogenic ★★ same condition
DLL3 p.Ala317fs Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Arg238Ter Pathogenic ★★ same condition
DLL3 p.Cys178Ter Likely pathogenic ★★ same condition
DLL3 p.Cys207fs Pathogenic ★★ same condition
DLL3 p.Cys207Ter Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Cys379Tyr Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Cys464_Glu465delinsTer 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/dll3-p-his447fs (accessed [today's date]).

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