NF2 p.Lys99fs
c.294del · VCV4759303
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
NF2-related schwannomatosis
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 3 of 16 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.3, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- NF2
- Protein
- p.Lys99fs
- Coding
- c.294del
- MANE Select
- NM_000268
- Type
- Deletion
- Location
- chr22:29639142 (GRCh38)
- Gene constraint
- LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.85 · 6 PDB
- Residue 99
- the ferm domain; a β-strand
Disease context
NF2-related schwannomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Full NF2-related schwannomatosis (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- NF2 p.Lys99Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- NF2 c.1447-147_1447-8del Likely pathogenic ★★ same condition
- NF2 p.Ala4fs Pathogenic ★★ same condition
- NF2 p.Lys449fs Pathogenic ★★ same condition
- NF2 p.Val92fs Pathogenic/Likely pathogenic ★★ same condition
- NF2 p.Leu551fs Uncertain significance ★★ same condition
- NF2 p.Met1_Ala4del Uncertain significance ★★ same condition
- NF2 c.810+23_810+25del Likely benign ★★ 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/nf2-p-lys99fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown