Is NF2 p.Ala6Asp (c.17C>A) pathogenic?

NF2 p.Ala6Asp (c.17C>A) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-15). AlphaMissense: likely pathogenic (0.9038); Very rare (popmax 6.95e-05%); Associated with NF2-related schwannomatosis.

What condition is associated with NF2 p.Ala6Asp (c.17C>A)?

NF2 p.Ala6Asp (c.17C>A) is associated with NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Ala6Asp (c.17C>A) in the general population?

NF2 p.Ala6Asp (c.17C>A) is very rare (popmax 6.95e-05%) (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.Ala6Asp (c.17C>A)?

AlphaMissense predicts likely pathogenic (score 0.9038) — an in-silico prediction, not a clinical call.

NF2 p.Ala6Asp

c.17C>A · rs2064713500 · VCV950781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9038 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.95e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

NF2-related schwannomatosis

Computational evidence

Protein change
AlphaMissense	0.9038	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 69 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 6.95e-05%

Overall 6.95e-05% 1/1,438,928 alleles · very rare

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.Ala6Asp
Coding: c.17C>A
MANE Select: NM_000268
dbSNP: rs2064713500
Type: single nucleotide variant
Location: chr22:29604015 (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.Ala6Phe Uncertain significance ★ same residue
NF2 p.Ala6Pro Uncertain significance ★ ⚠ same residue
NF2 p.Ala6Thr Uncertain significance ★ same residue
NF2 p.Ala6Val 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

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-ala6asp (accessed [today's date]).

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