Is DLL1 p.Pro51fs (c.150del) pathogenic?

DLL1 p.Pro51fs (c.150del) is classified Pathogenic in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Very rare (popmax 8.72e-05%, nfe).

How common is DLL1 p.Pro51fs (c.150del) in the general population?

DLL1 p.Pro51fs (c.150del) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

DLL1 p.Pro51fs

c.150del · VCV4526959

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

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 6.3	GERP -1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,660 alleles

Overall 7.16e-05% 1/1,396,540 alleles · very rare

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.Pro51fs
Coding: c.150del
MANE Select: NM_005618
Type: Deletion
Location: chr6:170289713 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 51: a UniProt-annotated variant site (in nedbas)

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

Similar variants

DLL1 p.Pro51= Likely benign ★ same residue
DLL1 p.Pro51Leu Benign ★ ⚠ same residue
DLL1 p.Glu673fs Pathogenic/Likely pathogenic ★★ same type
DLL1 p.Gly282fs Pathogenic/Likely pathogenic ★★ same type
DLL1 c.2167-3del Benign/Likely benign ★★ same type
DLL1 c.351+14del Likely benign ★★ same type
DLL1 p.Asp601_Ile602delinsVal Benign ★★ same type
DLL1 c.1033-22_1033-8del Pathogenic ★ same type

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-pro51fs (accessed [today's date]).

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