NF2 p.Gln333=
c.999G>A · rs1469191017 · VCV2587703
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.21 | loss · gain 0.02 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 22.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,846 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000274%
4/1,458,534 alleles · very rare
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
- NF2
- Protein
- p.Gln333=
- Coding
- c.999G>A
- MANE Select
- NM_000268
- dbSNP
- rs1469191017
- Type
- single nucleotide variant
- Location
- chr22:29668446 (GRCh38)
- Gene constraint
- LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.85 · 6 PDB
- Residue 333
- an α-helix
Similar variants
- NF2 p.Gln333His Uncertain significance ★★ same residue
- NF2 c.1575-2A>G Pathogenic ★★ same condition
- NF2 c.1737+1G>T Pathogenic ★★ same condition
- NF2 c.1737+2T>C Pathogenic/Likely pathogenic ★★ same condition
- NF2 c.240+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NF2 c.240+1G>C Pathogenic ★★ same condition
- NF2 c.240+1G>T Pathogenic/Likely pathogenic ★★ same condition
- NF2 c.363+2T>C Pathogenic/Likely 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/nf2-p-gln333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown