Is NF2 p.Phe498Ser (c.1493_1494delinsCT) pathogenic?

NF2 p.Phe498Ser (c.14931494delinsCT) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-12). Absent from gnomAD; Associated with NF2-related schwannomatosis.

What condition is associated with NF2 p.Phe498Ser (c.1493_1494delinsCT)?

NF2 p.Phe498Ser (c.1493_1494delinsCT) is associated with NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Phe498Ser (c.1493_1494delinsCT) in the general population?

NF2 p.Phe498Ser (c.1493_1494delinsCT) 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.Phe498Ser

c.1493_1494delinsCT · rs2147108238 · VCV1061051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0072 · regional, not allelic

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.Phe498Ser
Coding: c.1493_1494delinsCT
MANE Select: NM_000268
dbSNP: rs2147108238
Type: Indel
Location: chr22:29678242 (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

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.Phe498= Conflicting classifications of pathogenicity ★ same residue
NF2 p.Arg8Asn Uncertain significance ★★ same condition
NF2 p.Gln344fs Pathogenic ★ same condition
NF2 p.Glu107_Leu109delinsTer Pathogenic ★ same condition
NF2 p.Lys20fs Likely pathogenic ★ same condition
NF2 p.Val81fs Pathogenic ★ same condition
NF2 c.115-20_115-19delinsGT Uncertain significance ★ same condition
NF2 c.1738-4_1741delinsG Uncertain significance ★ 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-phe498ser (accessed [today's date]).

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