DLL3 p.Ile124=
c.372C>T · rs143468961 · VCV672989
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.28%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.57 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.2 | GERP -3.4 |
| Overall | ||
| CADD | 3.988 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.28%
African / African-American · 210/75,002 alleles
Filtering AF
0.249%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.237%
Overall
0.0149%
240/1,613,572 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.28% | 357 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,925 |
| Admixed American | 0.00833% | 12,000 |
| European (non-Finnish) | 0.00136% | 73,729 |
| South Asian | 0.0011% | 91,054 |
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.Ile124=
- Coding
- c.372C>T
- MANE Select
- NM_203486
- dbSNP
- rs143468961
- Type
- single nucleotide variant
- Location
- chr19:39500635 (GRCh38)
- Gene constraint
- LOEUF 1.512 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.42
Similar variants
- DLL3 c.652+1G>T Likely pathogenic ★★ same type
- DLL3 p.Arg221Ter Pathogenic ★★ same type
- DLL3 p.Arg238Ter Pathogenic ★★ same type
- DLL3 p.Cys178Ter Likely pathogenic ★★ same type
- DLL3 p.Cys207Ter Pathogenic/Likely pathogenic ★★ same type
- DLL3 p.Cys379Tyr Pathogenic/Likely pathogenic ★★ same type
- DLL3 p.Gln346Ter Pathogenic/Likely pathogenic ★★ same type
- DLL3 p.Gly504Asp Pathogenic/Likely pathogenic ★★ 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/dll3-p-ile124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown