Is DLL1 p.Cys452= (c.1356C>T) pathogenic?

DLL1 p.Cys452= (c.1356C>T) is classified Likely benign in DLL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-18). Very rare (popmax 0.00676%, eas); Associated with DLL1-related disorder.

What condition is associated with DLL1 p.Cys452= (c.1356C>T)?

DLL1 p.Cys452= (c.1356C>T) is associated with DLL1-related disorder (ClinVar).

How common is DLL1 p.Cys452= (c.1356C>T) in the general population?

DLL1 p.Cys452= (c.1356C>T) is very rare (popmax 0.00676%, eas) (gnomAD).

DLL1 p.Cys452=

c.1356C>T · rs148319460 · VCV3040225

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00676%, eas)

Conditions

DLL1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -4
Overall
CADD	0.376	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00676% East Asian · 3/44,368 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00188% 30/1,599,102 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00676%	14,789
African / African-American	0.00669%	14,944
Admixed American	0.00338%	29,543
South Asian	0.00223%	44,797
European (non-Finnish)	0.00153%	65,338

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DLL1
Protein: p.Cys452=
Coding: c.1356C>T
MANE Select: NM_005618
dbSNP: rs148319460
Type: single nucleotide variant
Location: chr6:170283923 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 452: the egf-like 7; calcium-binding domain; a disulfide bond; a UniProt-annotated variant site (in nedbas)

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

Disease context

DLL1-related disorder

Similar variants

DLL1 p.Gly475Asp Uncertain significance ★★ ⚠ same condition
DLL1 p.Pro95Ser Uncertain significance ★★ ⚠ same condition
DLL1 p.Val709Phe Uncertain significance ★★ ⚠ same condition
DLL1 p.Gln270Ter Likely pathogenic ★ same condition
DLL1 p.Pro261Leu Uncertain significance ★ ⚠ same condition
DLL1 p.Thr587Met Conflicting classifications of pathogenicity ★ ⚠ same condition
DLL1 p.Cys325Ter Likely pathogenic same condition
DLL1 p.Gly669Ala 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-cys452 (accessed [today's date]).

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