Is NF2 p.Phe498= (c.1494C>T) pathogenic?

NF2 p.Phe498= (c.1494C>T) is classified Conflicting classifications of pathogenicity in NF2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-16). Very rare (popmax 0.0022%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Phe498= (c.1494C>T)?

NF2 p.Phe498= (c.1494C>T) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Phe498= (c.1494C>T) in the general population?

NF2 p.Phe498= (c.1494C>T) is very rare (popmax 0.0022%, nfe) (gnomAD).

NF2 p.Phe498=

c.1494C>T · rs1060504990 · VCV417149

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Conditions

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 4	GERP 1, phastCons 1
Overall
CADD	14.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,180,010 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00167% 27/1,614,190 alleles · very rare exomes 27/1,461,846 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,385
Admixed American	0.00167%	60,024

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.Phe498=
Coding: c.1494C>T
MANE Select: NM_000268
dbSNP: rs1060504990
Type: single nucleotide variant
Location: chr22:29678243 (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.Phe498Cys Uncertain significance ★ ⚠ same residue
NF2 p.Phe498Val Uncertain significance ★ ⚠ same residue
NF2 p.Phe498Ser Uncertain significance ★ 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

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-phe498 (accessed [today's date]).

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