Is DLL3 p.Asp279Val (c.836A>T) pathogenic?

DLL3 p.Asp279Val (c.836A>T) is classified Uncertain significance in DLL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: ambiguous (0.3816); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DLL3 p.Asp279Val (c.836A>T)?

DLL3 p.Asp279Val (c.836A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLL3 p.Asp279Val (c.836A>T) in the general population?

DLL3 p.Asp279Val (c.836A>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about DLL3 p.Asp279Val (c.836A>T)?

AlphaMissense predicts ambiguous (score 0.3816) — an in-silico prediction, not a clinical call.

DLL3 p.Asp279Val

c.836A>T · rs1267360834 · VCV2492594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3816 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3816	ambiguous
REVEL	0.601	indeterminate
SaProt	LLR -5.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 9,279 bp · p 0.0035 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,032 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,932 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: DLL3
Protein: p.Asp279Val
Coding: c.836A>T
MANE Select: NM_203486
dbSNP: rs1267360834
Type: single nucleotide variant
Location: chr19:39504254 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42
Residue 279: a disulfide bond; the egf-like 2 domain

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.Asp279His Uncertain significance ★ ⚠ same residue
DLL3 p.Asp279Asn Uncertain significance ★ ⚠ same residue
DLL3 p.Asp279= 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

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-asp279val (accessed [today's date]).

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