DLL4 p.Pro52=
c.156C>T · rs367900130 · VCV722549
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0195%, nfe)
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 -0.37 | GERP -4.4, phastCons 0.081 |
| Overall | ||
| CADD | 11.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0195%
European (non-Finnish) · 230/1,179,812 alleles
Filtering AF
0.0174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0166%
Overall
0.0149%
241/1,612,946 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0195% | 5,130 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,919 |
| African / African-American | 0.00534% | 18,733 |
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.Pro52=
- Coding
- c.156C>T
- MANE Select
- NM_019074
- dbSNP
- rs367900130
- Type
- single nucleotide variant
- Location
- chr15:40929936 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
- Residue 52
- a disulfide bond; a β-strand
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-pro52 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown