Is CHRNB2 p.Ile112Val (c.334A>G) pathogenic?

CHRNB2 p.Ile112Val (c.334A>G) is classified Uncertain significance in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely benign (0.159); Absent from gnomAD v4.1.

How common is CHRNB2 p.Ile112Val (c.334A>G) in the general population?

CHRNB2 p.Ile112Val (c.334A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRNB2 p.Ile112Val (c.334A>G)?

AlphaMissense predicts likely benign (score 0.159) — an in-silico prediction, not a clinical call.

CHRNB2 p.Ile112Val

c.334A>G · VCV3769970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.159	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 3,773 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: CHRNB2
Protein: p.Ile112Val
Coding: c.334A>G
MANE Select: NM_000748
Type: single nucleotide variant
Location: chr1:154570336 (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

Similar variants

CHRNB2 p.Val287Leu Pathogenic/Likely pathogenic ★★ same type
CHRNB2 p.Val287Met Pathogenic ★★ same type
CHRNB2 p.Val308Ala Pathogenic/Likely pathogenic ★★ same type
CHRNB2 c.1338+3G>T Uncertain significance ★★ same type
CHRNB2 c.366-3C>T Uncertain significance ★★ same type
CHRNB2 p.Ala135Val Uncertain significance ★★ ⚠ same type
CHRNB2 p.Ala154Thr Uncertain significance ★★ ⚠ same type
CHRNB2 p.Ala207Gly Uncertain significance ★★ ⚠ same type

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-ile112val (accessed [today's date]).

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