Is DLL1 p.Arg509Ter (c.1525C>T) pathogenic?

DLL1 p.Arg509Ter (c.1525C>T) is classified Pathogenic in DLL1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-01-21). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures.

How common is DLL1 p.Arg509Ter (c.1525C>T) in the general population?

DLL1 p.Arg509Ter (c.1525C>T) is absent from gnomAD v4.1 (gnomAD).

DLL1 p.Arg509Ter

Q: What condition is associated with DLL1 p.Arg509Ter (c.1525C>T)?

DLL1 p.Arg509Ter (c.1525C>T) is associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (ClinVar).

c.1525C>T · rs1583152162 · VCV800562

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,573,504)

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -2.6, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,573,504). 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: DLL1
Protein: p.Arg509Ter
Coding: c.1525C>T
MANE Select: NM_005618
dbSNP: rs1583152162
Type: single nucleotide variant
Location: chr6:170283754 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 509: the egf-like 8 domain; a disulfide bond; a UniProt-annotated variant site (in nedbas); a UniProt-annotated variant site (in nedbas; uncertain significance)

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.Arg509Gln Uncertain significance ★ ⚠ same residue
DLL1 c.413-3T>G Uncertain significance ★★ same condition
DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg176Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg392Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg430His 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/dll1-p-arg509ter (accessed [today's date]).

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