DLL1 p.Ala433=
c.1299C>T · rs61757615 · VCV1604679
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.46%, 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 -5 | GERP -4 |
| Overall | ||
| CADD | 0.966 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.46%
South Asian · 3,038/87,810 alleles
Filtering AF
3.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.32%
Overall
0.241%
3,819/1,585,696 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 3.46% | 29 |
| Remaining individualsnot grpmax-eligible | 0.242% | 413 |
| Middle Eastern | 0.122% | 822 |
| Admixed American | 0.0976% | 1,024 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0752% | 1,330 |
| European (non-Finnish) | 0.0428% | 2,337 |
| African / African-American | 0.0403% | 2,483 |
| Finnishnot grpmax-eligible | 0.0219% | 4,567 |
| East Asian | 0.0115% | 8,713 |
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.Ala433=
- Coding
- c.1299C>T
- MANE Select
- NM_005618
- dbSNP
- rs61757615
- Type
- single nucleotide variant
- Location
- chr6:170283980 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24 · 1 PDB
- Residue 433
- the egf-like 6 domain; a disulfide bond; a UniProt-annotated variant site (in nedbas)
Similar variants
- DLL1 p.Ala433Pro Uncertain significance ★ ⚠ 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-ala433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown