Is DLL1 p.Val482Ile (c.1444G>A) pathogenic?

DLL1 p.Val482Ile (c.1444G>A) is classified Uncertain significance in DLL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0779); Ultra-rare (popmax 0.0332%, mid); Associated with Inborn genetic diseases.

What condition is associated with DLL1 p.Val482Ile (c.1444G>A)?

DLL1 p.Val482Ile (c.1444G>A) is associated with Inborn genetic diseases, neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (ClinVar).

How common is DLL1 p.Val482Ile (c.1444G>A) in the general population?

DLL1 p.Val482Ile (c.1444G>A) is ultra-rare (popmax 0.0332%, mid) (gnomAD).

What do computational predictors say about DLL1 p.Val482Ile (c.1444G>A)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

DLL1 p.Val482Ile

c.1444G>A · rs146638649 · VCV2440810

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -8.28	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 -1.6	GERP -0.52
Regional constraint	o/e 0.98	unconstrained · MANE · 2,388 bp · p 0.59 · regional, not allelic
Overall
CADD	6.631	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 0.0332% Middle Eastern · 2/6,024 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00131% 21/1,602,562 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,012
Admixed American	0.00504%	19,853
East Asian	0.0045%	22,244
African / African-American	0.00267%	37,451
Remaining individualsnot grpmax-eligible	0.00161%	62,106
South Asian	0.00111%	90,210
European (non-Finnish)	0.000849%	117,769

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.Val482Ile
Coding: c.1444G>A
MANE Select: NM_005618
dbSNP: rs146638649
Type: single nucleotide variant
Location: chr6:170283835 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 482: a UniProt-annotated variant site (in nedbas)

Full DLL1 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

Also linked: neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures

Similar variants

DLL1 p.Val482fs Likely pathogenic ★ same residue
DLL1 p.Arg509Ter Pathogenic ★★ same condition
DLL1 c.413-3T>G Uncertain significance ★★ same condition
DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala564Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg168His 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/dll1-p-val482ile (accessed [today's date]).

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