Is NF2 p.Asp508Glu (c.1524C>A) pathogenic?

NF2 p.Asp508Glu (c.1524C>A) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: ambiguous (0.489); Absent from gnomAD v4.1; Associated with NF2-related schwannomatosis.

What condition is associated with NF2 p.Asp508Glu (c.1524C>A)?

NF2 p.Asp508Glu (c.1524C>A) is associated with NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Asp508Glu (c.1524C>A) in the general population?

NF2 p.Asp508Glu (c.1524C>A) 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.

What do computational predictors say about NF2 p.Asp508Glu (c.1524C>A)?

AlphaMissense predicts ambiguous (score 0.489) — an in-silico prediction, not a clinical call.

NF2 p.Asp508Glu

c.1524C>A · VCV3675504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.489 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

NF2-related schwannomatosis

Computational evidence

Protein change
AlphaMissense	0.489	ambiguous
REVEL	0.562	indeterminate
SaProt	LLR -6.46	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.99, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0072 · regional, not allelic
Overall
CADD	23.1	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

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.Asp508Glu
Coding: c.1524C>A
MANE Select: NM_000268
Type: single nucleotide variant
Location: chr22:29678273 (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.Asp508His Uncertain significance ★★ ⚠ same residue
NF2 p.Asp508= Likely benign ★★ same residue
NF2 p.Asp508Asn Conflicting classifications of pathogenicity ★ same residue
NF2 p.Asp508Gly Uncertain significance ★ ⚠ same residue
NF2 p.Asp508Tyr 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

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-asp508glu (accessed [today's date]).

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