Is NF2 p.Pro482= (c.1446G>A) pathogenic?

NF2 p.Pro482= (c.1446G>A) is classified Conflicting classifications of pathogenicity in NF2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-07-09). Very rare (popmax 0.00208%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Pro482= (c.1446G>A)?

NF2 p.Pro482= (c.1446G>A) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis, familial meningioma (ClinVar).

How common is NF2 p.Pro482= (c.1446G>A) in the general population?

NF2 p.Pro482= (c.1446G>A) is very rare (popmax 0.00208%, nfe) (gnomAD).

NF2 p.Pro482=

c.1446G>A · rs753751373 · VCV412215

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00208%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.448	indeterminate
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Pangolin	Δ0.24	loss · gain 0.08 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 3.9	GERP -0.19, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00208% European (non-Finnish) · 24/1,151,138 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00167% 26/1,559,550 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00208%	47,964
Remaining individualsnot grpmax-eligible	0.00166%	60,416
South Asian	0.00118%	84,518

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.Pro482=
Coding: c.1446G>A
MANE Select: NM_000268
dbSNP: rs753751373
Type: single nucleotide variant
Location: chr22:29674941 (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.Pro482Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
NF2 p.Pro482Leu Conflicting classifications of pathogenicity ★ ⚠ 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
NF2 c.1737+1G>T 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-pro482 (accessed [today's date]).

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