Is CHRNB2 p.Phe99fs (c.297del) pathogenic?

CHRNB2 p.Phe99fs (c.297del) is classified Uncertain significance in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-14). Absent from gnomAD; Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNB2 p.Phe99fs (c.297del)?

CHRNB2 p.Phe99fs (c.297del) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNB2 p.Phe99fs (c.297del) in the general population?

CHRNB2 p.Phe99fs (c.297del) is absent from gnomAD (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CHRNB2 p.Phe99fs

c.297del · rs1696138351 · VCV1005287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.37	GERP -4, phastCons 0.97

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: CHRNB2
Protein: p.Phe99fs
Coding: c.297del
MANE Select: NM_000748
dbSNP: rs1696138351
Type: Deletion
Location: chr1:154570297 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB
Residue 99: an α-helix

Full CHRNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial sleep-related hypermotor epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sleep-related hypermotor epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CHRNB2 c.65-2del Uncertain significance ★★ same condition
CHRNB2 p.Cys245fs Uncertain significance ★★ same condition
CHRNB2 p.Cys470fs Uncertain significance ★★ same condition
CHRNB2 p.Glu371fs Uncertain significance ★★ same condition
CHRNB2 p.Val287_Pro289del Uncertain significance ★★ same condition
CHRNB2 p.Phe99= Benign/Likely benign ★★ same residue
CHRNB2 p.Asn392fs Uncertain significance ★ same condition
CHRNB2 p.Asp217fs 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/chrnb2-p-phe99fs (accessed [today's date]).

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