Is ADRB3 p.Ala184Pro (c.550G>C) pathogenic?

ADRB3 p.Ala184Pro (c.550G>C) is classified Uncertain significance in ADRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.0689); Absent from gnomAD v4.1.

How common is ADRB3 p.Ala184Pro (c.550G>C) in the general population?

ADRB3 p.Ala184Pro (c.550G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADRB3 p.Ala184Pro (c.550G>C)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

ADRB3 p.Ala184Pro

c.550G>C · VCV3502705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,082)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -4.12	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 3.1	GERP 0.57, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 2,248 bp · p 0.4 · regional, not allelic
Overall
CADD	21.0	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

No allele count reported in gnomAD v4.1 (AN 1,552,082). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADRB3
Protein: p.Ala184Pro
Coding: c.550G>C
MANE Select: NM_000025
Type: single nucleotide variant
Location: chr8:37965920 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.41 · 2 PDB
Residue 184: a disulfide bond

Full ADRB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADRB3 p.Asn338Ser Uncertain significance ★★ ⚠ same type
ADRB3 p.Lys151Arg Uncertain significance ★★ ⚠ same type
ADRB3 c.1205+14G>T Benign ★★ same type
ADRB3 c.1206-96A>G Benign ★★ same type
ADRB3 c.*250G>C Benign ★★ same type
ADRB3 p.Arg353Cys Benign ★★ ⚠ same type
ADRB3 p.Trp64Arg Benign ★★ same type
ADRB3 p.Ala130Thr 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/adrb3-p-ala184pro (accessed [today's date]).

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