VPS45 p.Lys296=
c.888G>A · rs1315600520 · VCV1336803
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
congenital neutropenia-myelofibrosis-nephromegaly syndrome
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 7.3 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- VPS45
- Protein
- p.Lys296=
- Coding
- c.888G>A
- MANE Select
- NM_007259
- dbSNP
- rs1315600520
- Type
- single nucleotide variant
- Location
- chr1:150081949 (GRCh38)
- Gene constraint
- LOEUF 0.629 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.65
Disease context
congenital neutropenia-myelofibrosis-nephromegaly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Congenital neutropenia-myelofibrosis-nephromegaly syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- VPS45 p.Lys296Asn Uncertain significance ★★ ⚠ same residue
- VPS45 p.Glu238Lys Likely pathogenic ★★ same condition
- VPS45 p.Thr224Asn Pathogenic ★★ same condition
- VPS45 c.687+5A>G Uncertain significance ★★ same condition
- VPS45 p.Ala392Thr Uncertain significance ★★ ⚠ same condition
- VPS45 p.Ala445Gly Uncertain significance ★★ ⚠ same condition
- VPS45 p.Ala567Val Uncertain significance ★★ ⚠ same condition
- VPS45 p.Arg148Gln Uncertain significance ★★ ⚠ 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/vps45-p-lys296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown