Is ADRB2 p.Gly280= (c.840C>T) pathogenic?

ADRB2 p.Gly280= (c.840C>T) is classified Likely benign in ADRB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-28). Rare (popmax 0.313%, afr); Associated with ADRB2-related disorder.

What condition is associated with ADRB2 p.Gly280= (c.840C>T)?

ADRB2 p.Gly280= (c.840C>T) is associated with ADRB2-related disorder (ClinVar).

How common is ADRB2 p.Gly280= (c.840C>T) in the general population?

ADRB2 p.Gly280= (c.840C>T) is rare (popmax 0.313%, afr) (gnomAD).

ADRB2 p.Gly280=

c.840C>T · rs35933628 · VCV3051710

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.313%, afr)

Conditions

ADRB2-related disorder

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 1.7, phastCons 1
Overall
CADD	13.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.313% African / African-American · 235/75,054 alleles

Filtering AF 0.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.267%

Overall 0.015% 242/1,614,180 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.313%	319
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,012
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.000169%	590,016

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: ADRB2
Protein: p.Gly280=
Coding: c.840C>T
MANE Select: NM_000024
dbSNP: rs35933628
Type: single nucleotide variant
Location: chr5:148827671 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.74 · 150 PDB
Residue 280: an α-helix

Full ADRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ADRB2-related disorder

Similar variants

ADRB2 p.Gly5Arg Uncertain significance ★ ⚠ same condition
ADRB2 p.Arg175= Benign ★★ same type
ADRB2 p.Gly351= Benign ★★ same type
ADRB2 p.Leu413= Benign ★★ same type
ADRB2 p.Leu84= Benign ★★ same type
ADRB2 p.Tyr366= Benign/Likely benign ★★ same type
ADRB2 p.Ala19Glu Uncertain significance ★ ⚠ same type
ADRB2 p.Arg328Trp 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/adrb2-p-gly280 (accessed [today's date]).

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