DLL1 p.Arg476=
c.1428G>A · rs375023006 · VCV2177952
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0515%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.19 | GERP -2, phastCons 0.072 |
| Overall | ||
| CADD | 9.888 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0515%
European (non-Finnish) · 607/1,178,680 alleles
Filtering AF
0.0481%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0467%
Overall
0.0392%
629/1,604,960 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0515% | 1,942 |
| Remaining individualsnot grpmax-eligible | 0.0193% | 5,185 |
| African / African-American | 0.012% | 8,320 |
| Finnishnot grpmax-eligible | 0.00174% | 57,554 |
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.Arg476=
- Coding
- c.1428G>A
- MANE Select
- NM_005618
- dbSNP
- rs375023006
- Type
- single nucleotide variant
- Location
- chr6:170283851 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24 · 1 PDB
- Residue 476
- the egf-like 7; calcium-binding domain; a disulfide bond; a UniProt-annotated variant site (in nedbas)
Similar variants
- DLL1 p.Arg509Ter Pathogenic ★★ same type
- DLL1 c.413-3T>G Uncertain significance ★★ same type
- DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala371Val Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala564Thr Uncertain significance ★★ ⚠ same type
- DLL1 p.Arg168His Uncertain significance ★★ ⚠ same type
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-arg476 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown