Is CHRNB2 p.Arg73Gln (c.218G>A) pathogenic?

CHRNB2 p.Arg73Gln (c.218G>A) is classified Uncertain significance in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: ambiguous (0.5166); Very rare (popmax 0.00333%, amr).

How common is CHRNB2 p.Arg73Gln (c.218G>A) in the general population?

CHRNB2 p.Arg73Gln (c.218G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CHRNB2 p.Arg73Gln (c.218G>A)?

AlphaMissense predicts ambiguous (score 0.5166) — an in-silico prediction, not a clinical call.

CHRNB2 p.Arg73Gln

c.218G>A · rs774455462 · VCV2500367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5166 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Computational evidence

Protein change
AlphaMissense	0.5166	ambiguous
REVEL	0.447	indeterminate
SaProt	LLR -8.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.95, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 3,773 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00062% 10/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
African / African-American	0.00267%	37,452
Finnishnot grpmax-eligible	0.00156%	64,024
European (non-Finnish)	0.000424%	236,007

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.Arg73Gln
Coding: c.218G>A
MANE Select: NM_000748
dbSNP: rs774455462
Type: single nucleotide variant
Location: chr1:154569799 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB
Residue 73: a turn

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

Similar variants

CHRNB2 p.Arg73Trp Uncertain significance ★★ ⚠ same residue
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

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-arg73gln (accessed [today's date]).

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