DLL1 p.Leu643=
c.1929C>T · rs758149257 · VCV2732397
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, 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 -0.48 | GERP -4, phastCons 0.016 |
| Overall | ||
| CADD | 6.413 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,874 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00329%
53/1,612,590 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,609 |
| Middle Eastern | 0.0164% | 6,084 |
| African / African-American | 0.00534% | 18,736 |
| South Asian | 0.00439% | 22,773 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| European (non-Finnish) | 0.00288% | 34,707 |
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.Leu643=
- Coding
- c.1929C>T
- MANE Select
- NM_005618
- dbSNP
- rs758149257
- Type
- single nucleotide variant
- Location
- chr6:170283350 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24 · 1 PDB
- Residue 643
- a UniProt-annotated variant site (in nedbas); a UniProt-annotated variant site (in nedbas; uncertain significance)
Similar variants
- 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
- DLL1 p.Arg168His 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-leu643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown