NOTCH2 p.Trp1463Leu
c.4387_4388delinsCT · rs2526147077 · VCV2856435
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Not reported
no gnomAD frequency available for this variant
Conditions
1
acroosteolysis dominant type
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.7 | phastCons 1 |
| Regional constraint | o/e 0.77 | unconstrained · MANE · 40 kb · p 1.4e-18 · regional, not allelic |
Population frequency
dbSNP / gnomAD
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- NOTCH2
- Protein
- p.Trp1463Leu
- Coding
- c.4387_4388delinsCT
- MANE Select
- NM_024408
- dbSNP
- rs2526147077
- Type
- Indel
- Location
- chr1:119925428 (GRCh38)
- Gene constraint
- LOEUF 0.151 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.51 · 2 PDB
- Residue 1463
- a turn; the 'negative regulatory region (nrr)' region
Similar variants
- NOTCH2 p.Cys1342_Gln1343delinsPheTer Pathogenic ★ same condition
- NOTCH2 p.Ser1708_Leu1711delinsTer Pathogenic ★ same condition
- NOTCH2 c.1681+13_1681+14delinsCA Uncertain significance ★ same condition
- NOTCH2 p.Arg1889fs Pathogenic ★★ same condition
- NOTCH2 p.Arg2003Ter Pathogenic/Likely pathogenic ★★ same condition
- NOTCH2 p.Arg2400Ter Pathogenic ★★ same condition
- NOTCH2 p.Gln2223Ter Pathogenic ★★ same condition
- NOTCH2 p.Gln2263Ter 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/notch2-p-trp1463leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown