DLL4 p.Ser224=
c.672G>A · rs61757617 · VCV713007
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.188%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.36 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.16 | GERP -1.6, phastCons 0.98 |
| Overall | ||
| CADD | 17.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.188%
European (non-Finnish) · 2,223/1,179,888 alleles
Filtering AF
0.182%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.179%
Overall
0.151%
2,443/1,613,956 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.188% | 531 |
| Middle Eastern | 0.181% | 551 |
| Remaining individualsnot grpmax-eligible | 0.125% | 801 |
| Admixed American | 0.0766% | 1,305 |
| African / African-American | 0.0493% | 2,027 |
| Finnishnot grpmax-eligible | 0.0312% | 3,201 |
| South Asian | 0.0285% | 3,503 |
| East Asian | 0.00446% | 22,440 |
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.Ser224=
- Coding
- c.672G>A
- MANE Select
- NM_019074
- dbSNP
- rs61757617
- Type
- single nucleotide variant
- Location
- chr15:40932184 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
- Residue 224
- a disulfide bond; the egf-like 1 domain
Similar variants
- DLL4 p.Ser224Leu 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-ser224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown