Is DLL3 p.Lys352Asn (c.1056G>T) pathogenic?

DLL3 p.Lys352Asn (c.1056G>T) is classified Uncertain significance in DLL3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.8688); Ultra-rare (popmax 0.0119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DLL3 p.Lys352Asn (c.1056G>T)?

DLL3 p.Lys352Asn (c.1056G>T) is associated with Inborn genetic diseases, spondylocostal dysostosis 1, autosomal recessive (ClinVar).

How common is DLL3 p.Lys352Asn (c.1056G>T) in the general population?

DLL3 p.Lys352Asn (c.1056G>T) is ultra-rare (popmax 0.0119%, nfe) (gnomAD).

What do computational predictors say about DLL3 p.Lys352Asn (c.1056G>T)?

AlphaMissense predicts likely pathogenic (score 0.8688) — an in-silico prediction, not a clinical call.

DLL3 p.Lys352Asn

c.1056G>T · rs376526613 · VCV1390694

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8688 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8688	likely pathogenic
REVEL	0.461	indeterminate
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 9,279 bp · p 0.0035 · regional, not allelic
Overall
CADD	25.2	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 0.0119% European (non-Finnish) · 141/1,180,022 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00972%

Overall 0.00898% 145/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0119%	8,369
African / African-American	0.00534%	18,730

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.Lys352Asn
Coding: c.1056G>T
MANE Select: NM_203486
dbSNP: rs376526613
Type: single nucleotide variant
Location: chr19:39505414 (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

Also linked: spondylocostal dysostosis 1, autosomal recessive

Similar variants

DLL3 p.Lys352= Likely benign ★ same residue
DLL3 c.652+1G>T Likely pathogenic ★★ same condition
DLL3 p.Arg238Ter Pathogenic ★★ same condition
DLL3 p.Cys178Ter Likely pathogenic ★★ same condition
DLL3 p.Cys207Ter Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Cys379Tyr Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Gln346Ter Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Gly504Asp Pathogenic/Likely pathogenic ★★ 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-lys352asn (accessed [today's date]).

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