Is NF2 p.Ala340= (c.1020T>C) pathogenic?

NF2 p.Ala340= (c.1020T>C) is classified Likely benign in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-23). Absent from gnomAD v4.1; Associated with NF2-related schwannomatosis.

What condition is associated with NF2 p.Ala340= (c.1020T>C)?

NF2 p.Ala340= (c.1020T>C) is associated with NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Ala340= (c.1020T>C) in the general population?

NF2 p.Ala340= (c.1020T>C) is absent from gnomAD v4.1 (gnomAD).

How is Full NF2-related schwannomatosis inherited?

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

NF2 p.Ala340=

c.1020T>C · rs1556000130 · VCV527712

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -4
Overall
CADD	5.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NF2
Protein: p.Ala340=
Coding: c.1020T>C
MANE Select: NM_000268
dbSNP: rs1556000130
Type: single nucleotide variant
Location: chr22:29671846 (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.Ala340Pro Uncertain significance ★ ⚠ same residue
NF2 p.Ala340Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
NF2 p.Ala340Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
NF2 p.Ala340fs Pathogenic ★ 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

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-ala340 (accessed [today's date]).

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