Is DLL3 p.Asp487Glu (c.1461C>A) pathogenic?

DLL3 p.Asp487Glu (c.1461C>A) is classified Uncertain significance in DLL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-03). AlphaMissense: likely benign (0.2393); Very rare (popmax 0.00188%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DLL3 p.Asp487Glu (c.1461C>A)?

DLL3 p.Asp487Glu (c.1461C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DLL3 p.Asp487Glu (c.1461C>A) in the general population?

DLL3 p.Asp487Glu (c.1461C>A) is very rare (popmax 0.00188%, nfe) (gnomAD).

What do computational predictors say about DLL3 p.Asp487Glu (c.1461C>A)?

AlphaMissense predicts likely benign (score 0.2393) — an in-silico prediction, not a clinical call.

DLL3 p.Asp487Glu

c.1461C>A · rs752572755 · VCV1519774

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2393 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00188%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2393	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.86	GERP -2.8
Regional constraint	o/e 1.10	unconstrained · MANE · 9,279 bp · p 0.0035 · regional, not allelic
Overall
CADD	14.08	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00188% European (non-Finnish) · 22/1,168,406 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00158% 25/1,585,632 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00188%	53,109
Finnishnot grpmax-eligible	0.00172%	58,212
Remaining individualsnot grpmax-eligible	0.00163%	61,376
African / African-American	0.00134%	74,378

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.Asp487Glu
Coding: c.1461C>A
MANE Select: NM_203486
dbSNP: rs752572755
Type: single nucleotide variant
Location: chr19:39507406 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL3 p.Asp487= Likely benign ★ same residue
DLL3 c.1758+20C>G Uncertain significance ★★ ⚠ same condition
DLL3 p.Ala139Thr Uncertain significance ★★ ⚠ same condition
DLL3 p.Ala446Val Uncertain significance ★★ ⚠ same condition
DLL3 p.Ala96Glu Uncertain significance ★★ ⚠ same condition
DLL3 p.Ala96Thr Uncertain significance ★★ ⚠ same condition
DLL3 p.Arg160Trp Uncertain significance ★★ ⚠ same condition
DLL3 p.Arg302Cys 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/dll3-p-asp487glu (accessed [today's date]).

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