Is ADRB3 p.Pro326= (c.978G>T) pathogenic?

ADRB3 p.Pro326= (c.978G>T) is classified Likely benign in ADRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-24). Very rare (popmax 0.00783%, amr).

How common is ADRB3 p.Pro326= (c.978G>T) in the general population?

ADRB3 p.Pro326= (c.978G>T) is very rare (popmax 0.00783%, amr) (gnomAD).

ADRB3 p.Pro326=

c.978G>T · rs780502227 · VCV748895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00783%, amr)

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 -0.64	GERP -5.2, phastCons 0.003
Overall
CADD	4.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00783% Admixed American · 4/51,088 alleles

Filtering AF 0.00263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00153%

Overall 0.000258% 4/1,552,018 alleles · very rare exomes 3/1,399,800 · genomes 1/152,218 · joint denominator

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.Pro326=
Coding: c.978G>T
MANE Select: NM_000025
dbSNP: rs780502227
Type: single nucleotide variant
Location: chr8:37965492 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.41 · 2 PDB
Residue 326: an α-helix

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

Similar variants

ADRB3 p.Pro326Ser Uncertain significance ★ ⚠ same residue
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

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-pro326 (accessed [today's date]).

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