Is DLL1 p.Arg61fs (c.181del) pathogenic?

DLL1 p.Arg61fs (c.181del) is classified Pathogenic in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). Associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures.

DLL1 p.Arg61fs

Q: What condition is associated with DLL1 p.Arg61fs (c.181del)?

DLL1 p.Arg61fs (c.181del) is associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (ClinVar).

c.181del · VCV3383967

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.54, phastCons 1

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

Variant & gene context

Gene: DLL1
Protein: p.Arg61fs
Coding: c.181del
MANE Select: NM_005618
Type: Deletion
Location: chr6:170289682 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 61: a UniProt-annotated variant site (in nedbas); a β-strand

Full DLL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL1 p.Glu673fs Pathogenic/Likely pathogenic ★★ same condition
DLL1 p.Gly282fs Pathogenic/Likely pathogenic ★★ same condition
DLL1 c.1250-8_1250-1del Likely pathogenic ★ same condition
DLL1 c.732-2del Likely pathogenic ★ same condition
DLL1 p.Ala418fs Pathogenic ★ same condition
DLL1 p.Arg635fs Likely pathogenic ★ same condition
DLL1 p.Cys496fs Likely pathogenic ★ same condition
DLL1 p.His295fs 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/dll1-p-arg61fs (accessed [today's date]).

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