Is NF2 p.Arg249Ter (c.745A>T) pathogenic?

NF2 p.Arg249Ter (c.745A>T) is classified Pathogenic in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-30). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Arg249Ter (c.745A>T)?

NF2 p.Arg249Ter (c.745A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF2 p.Arg249Ter (c.745A>T) in the general population?

NF2 p.Arg249Ter (c.745A>T) is absent from gnomAD v4.1 (gnomAD).

NF2 p.Arg249Ter

c.745A>T · rs2147009482 · VCV1759008

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.13, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Arg249Ter
Coding: c.745A>T
MANE Select: NM_000268
dbSNP: rs2147009482
Type: single nucleotide variant
Location: chr22:29661274 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 249: 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

Similar variants

NF2 p.Arg249Lys Uncertain significance ★ ⚠ same residue
NF2 p.Arg249= Likely benign ★ same residue
NF2 c.1575-2A>G Pathogenic ★★ same condition
NF2 c.1737+1G>T Pathogenic ★★ same condition
NF2 c.1737+2T>C Pathogenic/Likely pathogenic ★★ same condition
NF2 c.240+1G>A Pathogenic/Likely pathogenic ★★ same condition
NF2 c.240+1G>C Pathogenic ★★ same condition
NF2 c.240+1G>T Pathogenic/Likely 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-arg249ter (accessed [today's date]).

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