DLL1 p.Pro451=
c.1353G>T · rs374095083 · VCV2891488
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00225%, 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 -16 | GERP -3.6 |
| Overall | ||
| CADD | 0.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00225%
East Asian · 1/44,400 alleles
Filtering AF
0.000502%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000367%
Overall
0.00075%
12/1,599,138 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00225% | 44,400 |
| European (non-Finnish) | 0.000935% | 106,913 |
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
- DLL1
- Protein
- p.Pro451=
- Coding
- c.1353G>T
- MANE Select
- NM_005618
- dbSNP
- rs374095083
- Type
- single nucleotide variant
- Location
- chr6:170283926 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24 · 1 PDB
- Residue 451
- the egf-like 7; calcium-binding domain; a disulfide bond; a UniProt-annotated variant site (in nedbas)
Similar variants
- DLL1 p.Pro451Leu Benign ★★ ⚠ same residue
- DLL1 p.Arg509Ter Pathogenic ★★ same type
- DLL1 c.413-3T>G Uncertain significance ★★ same type
- DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala371Val Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same type
- DLL1 p.Ala564Thr 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/dll1-p-pro451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown