Is NF2 p.Ile5fs (c.12_22delinsTTCA) pathogenic?

NF2 p.Ile5fs (c.1222delinsTTCA) is classified Likely pathogenic in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Ile5fs (c.12_22delinsTTCA)?

NF2 p.Ile5fs (c.12_22delinsTTCA) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF2 p.Ile5fs (c.12_22delinsTTCA) in the general population?

NF2 p.Ile5fs (c.12_22delinsTTCA) is no gnomAD frequency available for this variant (gnomAD).

NF2 p.Ile5fs

c.12_22delinsTTCA · rs2518225830 · VCV2568067

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.1	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Ile5fs
Coding: c.12_22delinsTTCA
MANE Select: NM_000268
dbSNP: rs2518225830
Type: Indel
Location: chr22:29604010 (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.Ile5Met Uncertain significance ★★ ⚠ same residue
NF2 p.Ile5Val Uncertain significance ★★ ⚠ same residue
NF2 p.Ile5Thr Uncertain significance ★ same residue
NF2 p.Arg8Asn Uncertain significance ★★ same condition
NF2 p.Glu406Ter Pathogenic ★ same condition
NF2 c.517-8_517-3delinsATAC Uncertain significance ★ same condition
NF2 c.-4_-3delinsAA Uncertain significance ★ same condition
NF2 p.Glu379delinsHisCysAlaPro Uncertain significance ★ 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-ile5fs (accessed [today's date]).

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