Is NF2 p.Arg411fs (c.1229dup) pathogenic?

NF2 p.Arg411fs (c.1229dup) is classified Pathogenic in NF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Arg411fs (c.1229dup)?

NF2 p.Arg411fs (c.1229dup) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Arg411fs (c.1229dup) in the general population?

NF2 p.Arg411fs (c.1229dup) is absent from gnomAD (gnomAD).

NF2 p.Arg411fs

c.1229dup · rs2518680598 · VCV2054973

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 12 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NF2
Protein: p.Arg411fs
Coding: c.1229dup
MANE Select: NM_000268
dbSNP: rs2518680598
Type: Duplication
Location: chr22:29673374 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB

Full NF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: NF2-related schwannomatosis

Similar variants

NF2 p.Arg411Gly Uncertain significance ★★ ⚠ same residue
NF2 p.Arg411Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
NF2 p.Arg411His Conflicting classifications of pathogenicity ★ ⚠ same residue
NF2 p.Arg411= Likely benign ★ same residue
NF2 p.Arg336fs Pathogenic ★★ same condition
NF2 p.Ala451fs Pathogenic ★ same condition
NF2 p.Arg160fs Pathogenic ★ same condition
NF2 p.Arg353fs 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-arg411fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown