Is ADRB3 p.Arg236Pro (c.707G>C) pathogenic?

ADRB3 p.Arg236Pro (c.707G>C) is classified Uncertain significance in ADRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). AlphaMissense: likely benign (0.2869); Very rare (popmax 0.0012%, sas).

How common is ADRB3 p.Arg236Pro (c.707G>C) in the general population?

ADRB3 p.Arg236Pro (c.707G>C) is very rare (popmax 0.0012%, sas) (gnomAD).

What do computational predictors say about ADRB3 p.Arg236Pro (c.707G>C)?

AlphaMissense predicts likely benign (score 0.2869) — an in-silico prediction, not a clinical call.

ADRB3 p.Arg236Pro

c.707G>C · VCV3502669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2869	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -14.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.72	GERP -1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 2,248 bp · p 0.4 · regional, not allelic
Overall
CADD	24.3	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 0.0012% South Asian · 1/83,524 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000193% 3/1,550,514 alleles · very rare exomes 2/1,398,212 · genomes 1/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0012%	83,524
European (non-Finnish)	0.000174%	573,401

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: ADRB3
Protein: p.Arg236Pro
Coding: c.707G>C
MANE Select: NM_000025
Type: single nucleotide variant
Location: chr8:37965763 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.41 · 2 PDB
Residue 236: an α-helix

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

Similar variants

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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-arg236pro (accessed [today's date]).

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