Is NF2 p.Lys294= (c.882G>A) pathogenic?

NF2 p.Lys294= (c.882G>A) is classified Likely benign in NF2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0847%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Lys294= (c.882G>A)?

NF2 p.Lys294= (c.882G>A) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Lys294= (c.882G>A) in the general population?

NF2 p.Lys294= (c.882G>A) is ultra-rare (popmax 0.0847%, eas) (gnomAD).

NF2 p.Lys294=

c.882G>A · rs146166875 · VCV457929

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, eas)

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 1.9	GERP -2.6, phastCons 1
Overall
CADD	6.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0847% East Asian · 38/44,884 alleles

Filtering AF 0.0634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.056%

Overall 0.0026% 42/1,612,388 alleles · ultra-rare exomes 38/1,460,078 · genomes 4/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0847%	1,181
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)	8.49e-05%	1,178,425

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.Lys294=
Coding: c.882G>A
MANE Select: NM_000268
dbSNP: rs146166875
Type: single nucleotide variant
Location: chr22:29665061 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 294: the ferm domain; an α-helix

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.Lys294Gln 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
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

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-lys294 (accessed [today's date]).

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