Is DLL1 p.Phe191fs (c.543_570dup) pathogenic?

DLL1 p.Phe191fs (c.543570dup) is classified Pathogenic in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-01). Absent from gnomAD.

How common is DLL1 p.Phe191fs (c.543_570dup) in the general population?

DLL1 p.Phe191fs (c.543_570dup) is absent from gnomAD (gnomAD).

DLL1 p.Phe191fs

c.543_570dup · rs1554273585 · VCV524108

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

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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, 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: DLL1
Protein: p.Phe191fs
Coding: c.543_570dup
MANE Select: NM_005618
dbSNP: rs1554273585
Type: Duplication
Location: chr6:170288338 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 191: the dsl domain; 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.Phe191= Likely benign ★★ same residue
DLL1 p.Ala528fs Likely pathogenic ★★ same type
DLL1 p.Cys274_Asn275insThrCysGlnGlnProTrpGlnCys Uncertain significance ★★ same type
DLL1 p.Arg193fs Pathogenic ★ same type
DLL1 p.Asn41fs Likely pathogenic ★ same type
DLL1 p.Glu209fs Likely pathogenic ★ same type
DLL1 p.Glu74fs Likely pathogenic ★ same type
DLL1 p.Gly235fs 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-phe191fs (accessed [today's date]).

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