Is ADRB2 p.Ala19Glu (c.56C>A) pathogenic?

ADRB2 p.Ala19Glu (c.56C>A) is classified Uncertain significance in ADRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.0827); Ultra-rare (popmax 0.0111%, eas).

How common is ADRB2 p.Ala19Glu (c.56C>A) in the general population?

ADRB2 p.Ala19Glu (c.56C>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about ADRB2 p.Ala19Glu (c.56C>A)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

ADRB2 p.Ala19Glu

c.56C>A · rs765494455 · VCV2511448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.7, phastCons 0.46
Regional constraint	o/e 0.79	unconstrained · MANE · 920 bp · p 2.2e-05 · regional, not allelic
Overall
CADD	16.21	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

Grpmax group 0.0111% East Asian · 5/44,872 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000558% 9/1,613,770 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,974
European (non-Finnish)	0.000339%	295,013

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.Ala19Glu
Coding: c.56C>A
MANE Select: NM_000024
dbSNP: rs765494455
Type: single nucleotide variant
Location: chr5:148826887 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.74 · 150 PDB

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

Similar variants

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.Arg328Trp Uncertain significance ★ ⚠ same type
ADRB2 p.Gln3Lys Uncertain significance ★ ⚠ same type
ADRB2 p.Glu62Asp 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-ala19glu (accessed [today's date]).

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