DLL4 p.His358=
c.1074T>C · rs28568593 · VCV788805
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.48%, afr)
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 0.23 | GERP -4.3, phastCons 0.98 |
| Overall | ||
| CADD | 7.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.48%
African / African-American · 2,612/75,052 alleles
Filtering AF
3.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.32%
Overall
0.858%
13,847/1,613,742 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.48% | 29 |
| Middle Eastern | 2.19% | 46 |
| Ashkenazi Jewishnot grpmax-eligible | 1.72% | 58 |
| Admixed American | 0.993% | 101 |
| Remaining individualsnot grpmax-eligible | 0.928% | 108 |
| Finnishnot grpmax-eligible | 0.769% | 130 |
| European (non-Finnish) | 0.732% | 137 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| South Asian | 0.316% | 316 |
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.His358=
- Coding
- c.1074T>C
- MANE Select
- NM_019074
- dbSNP
- rs28568593
- Type
- single nucleotide variant
- Location
- chr15:40934951 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
- Residue 358
- a disulfide bond; the egf-like 4 domain
Similar variants
- DLL4 p.His358Tyr Uncertain significance ★ ⚠ same residue
- 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
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-his358 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown