DLL1 p.His487=
c.1461C>T · rs148030321 · VCV727464
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0949%, amr)
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 -6.5 | GERP -4 |
| Overall | ||
| CADD | 2.821 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0949%
Admixed American · 55/57,928 alleles
Filtering AF
0.0749%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0677%
Overall
0.0107%
171/1,592,070 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0949% | 1,053 |
| East Asian | 0.0506% | 1,976 |
| Middle Eastern | 0.0498% | 2,010 |
| South Asian | 0.0146% | 6,838 |
| Remaining individualsnot grpmax-eligible | 0.0146% | 6,852 |
| European (non-Finnish) | 0.00554% | 18,045 |
| African / African-American | 0.00402% | 24,856 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,314 |
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.His487=
- Coding
- c.1461C>T
- MANE Select
- NM_005618
- dbSNP
- rs148030321
- Type
- single nucleotide variant
- Location
- chr6:170283818 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24 · 1 PDB
- Residue 487
- the egf-like 8 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-his487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown