Is NF2 p.Arg447Ser (c.1341G>T) pathogenic?

NF2 p.Arg447Ser (c.1341G>T) is classified Uncertain significance in NF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-02). AlphaMissense: likely pathogenic (0.9862); No allele count reported in gnomAD v4.1 (AN 1,555,152); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Arg447Ser (c.1341G>T)?

NF2 p.Arg447Ser (c.1341G>T) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis, familial meningioma (ClinVar).

How common is NF2 p.Arg447Ser (c.1341G>T) in the general population?

NF2 p.Arg447Ser (c.1341G>T) is no allele count reported in gnomAD v4.1 (AN 1,555,152) (gnomAD).

What do computational predictors say about NF2 p.Arg447Ser (c.1341G>T)?

AlphaMissense predicts likely pathogenic (score 0.9862) — an in-silico prediction, not a clinical call.

NF2 p.Arg447Ser

c.1341G>T · rs2066911364 · VCV1770382

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9862 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,555,152)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9862	likely pathogenic
REVEL	0.68	pathogenic-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0072 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,555,152). 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.Arg447Ser
Coding: c.1341G>T
MANE Select: NM_000268
dbSNP: rs2066911364
Type: single nucleotide variant
Location: chr22:29674836 (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 familial meningioma

Similar variants

NF2 p.Arg447Met Uncertain significance ★★ ⚠ same residue
NF2 p.Arg447= Likely benign ★★ same residue
NF2 p.Arg447Gly 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-arg447ser (accessed [today's date]).

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