DLL4 p.Pro524=
c.1572G>A · rs550859837 · VCV1984019
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0938%, 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 -2.7 | GERP -5.3 |
| Overall | ||
| CADD | 2.192 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0938%
South Asian · 85/90,592 alleles
Filtering AF
0.0777%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0717%
Overall
0.00634%
102/1,609,328 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0938% | 1,066 |
| African / African-American | 0.00534% | 18,740 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,785 |
| European (non-Finnish) | 0.000849% | 117,851 |
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.Pro524=
- Coding
- c.1572G>A
- MANE Select
- NM_019074
- dbSNP
- rs550859837
- Type
- single nucleotide variant
- Location
- chr15:40936559 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
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-pro524 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown