DLL1 p.Cys549=
c.1647C>T · rs367852951 · VCV1593455
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0265%, 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 -4.1 | GERP -4 |
| Overall | ||
| CADD | 0.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0265%
South Asian · 24/90,658 alleles
Filtering AF
0.0182%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0155%
Overall
0.0123%
197/1,606,560 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0265% | 3,777 |
| East Asian | 0.0224% | 4,472 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,768 |
| European (non-Finnish) | 0.0126% | 7,948 |
| Admixed American | 0.00671% | 14,913 |
| African / African-American | 0.00267% | 37,459 |
| Finnishnot grpmax-eligible | 0.00161% | 61,932 |
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.Cys549=
- Coding
- c.1647C>T
- MANE Select
- NM_005618
- dbSNP
- rs367852951
- Type
- single nucleotide variant
- Location
- chr6:170283632 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24 · 1 PDB
- Residue 549
- a UniProt-annotated variant site (in nedbas); a UniProt-annotated variant site (in nedbas; uncertain significance)
Similar variants
- DLL1 p.Cys549Ter Pathogenic ★ 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-cys549 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown