Is NF2 p.Ala489del (c.1465_1467del) pathogenic?

NF2 p.Ala489del (c.14651467del) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Ala489del (c.1465_1467del)?

NF2 p.Ala489del (c.1465_1467del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF2 p.Ala489del (c.1465_1467del) in the general population?

NF2 p.Ala489del (c.1465_1467del) is absent from gnomAD (gnomAD).

NF2 p.Ala489del

c.1465_1467del · rs1601658938 · VCV819187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 2, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala489del
Coding: c.1465_1467del
MANE Select: NM_000268
dbSNP: rs1601658938
Type: Deletion
Location: chr22:29678212 (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

Similar variants

NF2 p.Ala489Val Uncertain significance ★★ ⚠ same residue
NF2 p.Ala489Glu Uncertain significance ★ ⚠ same residue
NF2 c.1447-147_1447-8del Likely pathogenic ★★ same condition
NF2 p.Leu551fs Uncertain significance ★★ same condition
NF2 p.Met1_Ala4del Uncertain significance ★★ same condition
NF2 c.810+23_810+25del Likely benign ★★ same condition
NF2 p.Asp503fs Pathogenic ★ same condition
NF2 p.Asp513_Met514insTer 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-ala489del (accessed [today's date]).

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