NF1 p.Pro22fs
c.65del · VCV4735628
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
neurofibromatosis type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 58 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- NF1
- Protein
- p.Pro22fs
- Coding
- c.65del
- MANE Select
- NM_001042492
- Type
- Deletion
- Location
- chr17:31155986 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Disease context
neurofibromatosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Neurofibromatosis type 1 (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Infancy, Neonatal
- Prevalence
- 1-5 / 10 000 (United Kingdom)
Similar variants
- NF1 p.Pro22Leu Uncertain significance ★★ same residue
- NF1 p.Pro22= Likely benign ★★ same residue
- NF1 p.Pro22Ala Uncertain significance ★ same residue
- NF1 p.Pro22Ser Conflicting classifications of pathogenicity ★ same residue
- NF1 p.Pro22_Ile23insTer Pathogenic ★ same residue
- NF1 c.1183_1185+2del Pathogenic/Likely pathogenic ★★ same condition
- NF1 c.1392+2del Pathogenic/Likely pathogenic ★★ same condition
- NF1 c.1527+1del 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/nf1-p-pro22fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown