DLL3 p.Pro181=
c.543T>C · rs115194365 · VCV386780
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.79%, afr)
Conditions
1
spondylocostal dysostosis 1, autosomal recessive
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 -8.4 | GERP -2.5 |
| Overall | ||
| CADD | 0.929 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.79%
African / African-American · 1,208/67,426 alleles
Filtering AF
1.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.67%
Overall
0.0975%
1,410/1,445,684 alleles · low-frequency
exomes 639/1,293,612 · genomes 771/152,072 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.79% | 56 |
| Admixed American | 0.141% | 708 |
| Remaining individualsnot grpmax-eligible | 0.139% | 720 |
| Middle Eastern | 0.0737% | 1,357 |
| East Asian | 0.00901% | 11,103 |
| European (non-Finnish) | 0.00588% | 17,010 |
| South Asian | 0.00272% | 36,789 |
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
- DLL3
- Protein
- p.Pro181=
- Coding
- c.543T>C
- MANE Select
- NM_203486
- dbSNP
- rs115194365
- Type
- single nucleotide variant
- Location
- chr19:39502948 (GRCh38)
- Gene constraint
- LOEUF 1.512 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.42
- Residue 181
- the dsl domain
Similar variants
- DLL3 p.Pro181Leu Uncertain significance ★ ⚠ same residue
- DLL3 c.652+1G>T Likely pathogenic ★★ same condition
- DLL3 p.Arg238Ter Pathogenic ★★ same condition
- DLL3 p.Cys178Ter Likely pathogenic ★★ same condition
- DLL3 p.Cys207Ter Pathogenic/Likely pathogenic ★★ same condition
- DLL3 p.Cys379Tyr Pathogenic/Likely pathogenic ★★ same condition
- DLL3 p.Gln346Ter Pathogenic/Likely pathogenic ★★ same condition
- DLL3 p.Gly504Asp Pathogenic/Likely pathogenic ★★ same condition
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/dll3-p-pro181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown