Is DLL3 p.Arg177fs (c.530_531del) pathogenic?

DLL3 p.Arg177fs (c.530531del) is classified Pathogenic in DLL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Very rare (popmax 0.00275%, sas).

How common is DLL3 p.Arg177fs (c.530_531del) in the general population?

DLL3 p.Arg177fs (c.530_531del) is very rare (popmax 0.00275%, sas) (gnomAD).

DLL3 p.Arg177fs

c.530_531del · rs1271691132 · VCV1457773

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00275%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 0.33, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00275% South Asian · 2/72,746 alleles

Filtering AF 0.000456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000171%

Overall 0.000698% 9/1,288,508 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00275%	36,373
Remaining individualsnot grpmax-eligible	0.00181%	55,208
European (non-Finnish)	0.000544%	183,795

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: DLL3
Protein: p.Arg177fs
Coding: c.530_531del
MANE Select: NM_203486
dbSNP: rs1271691132
Type: Microsatellite
Location: chr19:39502928 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42
Residue 177: the dsl domain

Full DLL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLL3 p.Arg177= Conflicting classifications of pathogenicity ★ same residue
DLL3 p.Cys464_Glu465delinsTer Pathogenic ★★ same type
DLL3 p.Pro202fs Pathogenic ★★ same type
DLL3 p.Arg380_Ala381insCysArg Uncertain significance ★ same type
DLL3 c.1093+3GAGGCCTG[3] Likely benign ★ 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/dll3-p-arg177fs (accessed [today's date]).

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