NF2 p.Glu404=
c.1212G>A · rs748403377 · VCV700785
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, sas)
Conditions
2
hereditary neoplastic 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 2.5 | GERP -0.14, phastCons 1 |
| Overall | ||
| CADD | 8.846 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
South Asian · 12/89,454 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00603%
Overall
0.000808%
13/1,608,250 alleles · ultra-rare
exomes 13/1,455,860 · genomes 0/152,390 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0134% | 7,455 |
| European (non-Finnish) | 8.49e-05% | 1,177,890 |
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.Glu404=
- Coding
- c.1212G>A
- MANE Select
- NM_000268
- dbSNP
- rs748403377
- Type
- single nucleotide variant
- Location
- chr22:29673358 (GRCh38)
- Gene constraint
- LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.85 · 6 PDB
Similar variants
- NF2 p.Glu404Ter Pathogenic ★ same residue
- NF2 c.115-1G>A Likely pathogenic ★★ same condition
- NF2 c.1340+1G>T Pathogenic ★★ same condition
- NF2 c.1340+2T>G Pathogenic ★★ same condition
- NF2 c.1447-1G>A Pathogenic ★★ same condition
- 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
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-glu404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown