DLL4 p.His440=
c.1320C>T · rs370793294 · VCV2182187
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.041%, sas)
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 -0.15 | GERP -1.9 |
| Overall | ||
| CADD | 4.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.041%
South Asian · 37/90,194 alleles
Filtering AF
0.0306%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0269%
Overall
0.0157%
252/1,609,176 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.041% | 2,438 |
| European (non-Finnish) | 0.017% | 5,891 |
| Middle Eastern | 0.0166% | 6,032 |
| African / African-American | 0.00933% | 10,713 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,786 |
| Finnishnot grpmax-eligible | 0.00319% | 31,321 |
| East Asian | 0.00224% | 44,736 |
| Admixed American | 0.00168% | 59,554 |
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
- DLL4
- Protein
- p.His440=
- Coding
- c.1320C>T
- MANE Select
- NM_019074
- dbSNP
- rs370793294
- Type
- single nucleotide variant
- Location
- chr15:40936307 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
- Residue 440
- the egf-like 7 domain
Similar variants
- DLL4 p.Cys390Tyr Pathogenic/Likely pathogenic ★★ same type
- DLL4 p.Cys466Arg Likely pathogenic ★★ same type
- DLL4 p.Gln584Ter Pathogenic/Likely pathogenic ★★ same type
- DLL4 p.Ala450Val Uncertain significance ★★ ⚠ same type
- DLL4 p.Arg186His Uncertain significance ★★ ⚠ same type
- DLL4 p.Arg313Cys Uncertain significance ★★ ⚠ same type
- DLL4 p.Arg645Gln Uncertain significance ★★ ⚠ same type
- DLL4 p.Asn381Lys 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/dll4-p-his440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown