Is DLL3 p.Arg160Trp (c.478C>T) pathogenic?

DLL3 p.Arg160Trp (c.478C>T) is classified Uncertain significance in DLL3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-26). AlphaMissense: likely benign (0.1914); Ultra-rare (popmax 0.0212%, eas); Associated with Inborn genetic diseases.

What condition is associated with DLL3 p.Arg160Trp (c.478C>T)?

DLL3 p.Arg160Trp (c.478C>T) is associated with Inborn genetic diseases, spondylocostal dysostosis 1, autosomal recessive, syndactyly (ClinVar).

How common is DLL3 p.Arg160Trp (c.478C>T) in the general population?

DLL3 p.Arg160Trp (c.478C>T) is ultra-rare (popmax 0.0212%, eas) (gnomAD).

What do computational predictors say about DLL3 p.Arg160Trp (c.478C>T)?

AlphaMissense predicts likely benign (score 0.1914) — an in-silico prediction, not a clinical call.

DLL3 p.Arg160Trp

c.478C>T · rs376907733 · VCV894146

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1914 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0212%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1914	likely benign
REVEL	0.563	indeterminate
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.33, phastCons 0.69
Regional constraint	o/e 1.10	unconstrained · MANE · 9,279 bp · p 0.0035 · regional, not allelic
Overall
CADD	24.8	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 0.0212% East Asian · 7/33,062 alleles

Filtering AF 0.00986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00702%

Overall 0.0034% 49/1,439,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0212%	4,723
Remaining individualsnot grpmax-eligible	0.0181%	5,521
Ashkenazi Jewishnot grpmax-eligible	0.00397%	25,220
European (non-Finnish)	0.00272%	36,739
South Asian	0.00138%	72,572

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.Arg160Trp
Coding: c.478C>T
MANE Select: NM_203486
dbSNP: rs376907733
Type: single nucleotide variant
Location: chr19:39502883 (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 syndactyly

Similar variants

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
DLL3 c.1758+20C>G 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-arg160trp (accessed [today's date]).

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