Is CHRNB2 p.Cys356Ter (c.1068C>A) pathogenic?

CHRNB2 p.Cys356Ter (c.1068C>A) is classified Uncertain significance in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-10). Very rare (popmax 8.54e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHRNB2 p.Cys356Ter (c.1068C>A)?

CHRNB2 p.Cys356Ter (c.1068C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CHRNB2 p.Cys356Ter (c.1068C>A) in the general population?

CHRNB2 p.Cys356Ter (c.1068C>A) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

CHRNB2 p.Cys356Ter

c.1068C>A · rs762237464 · VCV589945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Conditions

Inborn genetic diseases

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
NMD	predicted	premature termination codon in exon 5 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.4
Overall
CADD	32.0	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

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,170,628 alleles

Overall 6.97e-05% 1/1,434,950 alleles · very rare

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: CHRNB2
Protein: p.Cys356Ter
Coding: c.1068C>A
MANE Select: NM_000748
dbSNP: rs762237464
Type: single nucleotide variant
Location: chr1:154571891 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRNB2 p.Cys356= Likely benign ★ same residue
CHRNB2 p.Ala2Ser Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Arg3Trp Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Asn392Lys Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Gly430Ser Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Ile434Met Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Ser440Arg Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Thr57Ile 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-cys356ter (accessed [today's date]).

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