DLL4 p.His123=
c.369C>T · rs187700175 · VCV731630
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.67%, 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 2.2 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 12.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.67%
South Asian · 1,523/91,058 alleles
Filtering AF
1.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.57%
Overall
0.384%
6,196/1,613,834 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.67% | 60 |
| Middle Eastern | 0.66% | 152 |
| Finnishnot grpmax-eligible | 0.504% | 198 |
| Remaining individualsnot grpmax-eligible | 0.376% | 266 |
| European (non-Finnish) | 0.333% | 300 |
| Admixed American | 0.145% | 690 |
| African / African-American | 0.0666% | 1,501 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0236% | 4,229 |
| East Asian | 0.00891% | 11,222 |
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.His123=
- Coding
- c.369C>T
- MANE Select
- NM_019074
- dbSNP
- rs187700175
- Type
- single nucleotide variant
- Location
- chr15:40930657 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.89 · 1 PDB
- Residue 123
- 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-his123 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown