Is NF2 p.Ile26= (c.78C>T) pathogenic?

NF2 p.Ile26= (c.78C>T) is classified Likely benign in NF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-28). Very rare (popmax 0.00051%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Ile26= (c.78C>T)?

NF2 p.Ile26= (c.78C>T) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Ile26= (c.78C>T) in the general population?

NF2 p.Ile26= (c.78C>T) is very rare (popmax 0.00051%, nfe) (gnomAD).

NF2 p.Ile26=

c.78C>T · rs2064716954 · VCV1113514

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP 1.7, phastCons 0.99
Overall
CADD	14.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00051% European (non-Finnish) · 6/1,177,298 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000373% 6/1,607,814 alleles · very rare exomes 6/1,455,458 · genomes 0/152,356 · joint denominator

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.Ile26=
Coding: c.78C>T
MANE Select: NM_000268
dbSNP: rs2064716954
Type: single nucleotide variant
Location: chr22:29604076 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 26: the ferm domain; a β-strand

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

Also linked: NF2-related schwannomatosis

Similar variants

NF2 p.Ile26Thr Uncertain significance ★★ ⚠ same residue
NF2 p.Ile26Val Uncertain significance ★★ ⚠ same residue
NF2 p.Ile26Met Uncertain significance ★ ⚠ same residue
NF2 p.Ile26Phe 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-ile26 (accessed [today's date]).

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