DLL4 p.Ser533=
c.1599G>A · VCV3717787
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
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 -0.47 | GERP -5.3, phastCons 0.03 |
| Overall | ||
| CADD | 8.646 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,722 alleles
Filtering AF
0.0116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.0111%
178/1,609,070 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,969 |
| European (non-Finnish) | 0.0133% | 7,506 |
| African / African-American | 0.0107% | 9,374 |
| Admixed American | 0.00168% | 59,374 |
| Finnishnot grpmax-eligible | 0.00161% | 62,116 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,346 |
| South Asian | 0.0011% | 90,658 |
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.Ser533=
- Coding
- c.1599G>A
- MANE Select
- NM_019074
- Type
- single nucleotide variant
- Location
- chr15:40936586 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
Similar variants
- DLL4 p.Ser533Leu 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-ser533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown