Is NF2 p.Arg554fs (c.1660_1661del) pathogenic?

NF2 p.Arg554fs (c.16601661del) is classified Pathogenic in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). Absent from gnomAD; Associated with NF2-related schwannomatosis.

What condition is associated with NF2 p.Arg554fs (c.1660_1661del)?

NF2 p.Arg554fs (c.1660_1661del) is associated with NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Arg554fs (c.1660_1661del) in the general population?

NF2 p.Arg554fs (c.1660_1661del) is absent from gnomAD (gnomAD).

How is Full NF2-related schwannomatosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

NF2 p.Arg554fs

c.1660_1661del · rs1601666191 · VCV649883

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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 15 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	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.Arg554fs
Coding: c.1660_1661del
MANE Select: NM_000268
dbSNP: rs1601666191
Type: Microsatellite
Location: chr22:29681520 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 554: an α-helix

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

Disease context

NF2-related schwannomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Full NF2-related schwannomatosis (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

NF2 p.Arg554Gly Uncertain significance ★★ same residue
NF2 p.Arg554Lys Uncertain significance ★★ ⚠ same residue
NF2 p.Arg554Thr Uncertain significance ★★ ⚠ same residue
NF2 p.Arg554= Likely benign ★★ same residue
NF2 p.Arg554Trp Uncertain significance ★ ⚠ same residue
NF2 p.Arg187fs Pathogenic/Likely pathogenic ★★ same condition
NF2 p.Glu445fs Pathogenic ★★ same condition
NF2 p.Phe119del 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-arg554fs (accessed [today's date]).

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