Is ADRB1 p.Pro355= (c.1065C>A) pathogenic?

ADRB1 p.Pro355= (c.1065C>A) is classified Benign in ADRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-08). Rare (popmax 0.335%, nfe).

How common is ADRB1 p.Pro355= (c.1065C>A) in the general population?

ADRB1 p.Pro355= (c.1065C>A) is rare (popmax 0.335%, nfe) (gnomAD).

ADRB1 p.Pro355=

c.1065C>A · rs141633952 · VCV789895

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.335%, nfe)

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 -4.7	GERP -3.6
Overall
CADD	5.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.335% European (non-Finnish) · 3,925/1,172,038 alleles

Filtering AF 0.326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.323%

Overall 0.291% 4,648/1,598,152 alleles · rare exomes 4,400/1,447,276 · genomes 248/150,876 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.603%	166
European (non-Finnish)grpmax	0.335%	299
Remaining individualsnot grpmax-eligible	0.28%	357
South Asian	0.276%	363
Admixed American	0.125%	800
Middle Eastern	0.0664%	1,506
African / African-American	0.0566%	1,768
Finnishnot grpmax-eligible	0.0113%	8,854
East Asian	0.00228%	43,924

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ADRB1
Protein: p.Pro355=
Coding: c.1065C>A
MANE Select: NM_000684
dbSNP: rs141633952
Type: single nucleotide variant
Location: chr10:114045197 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 77.01 · 7 PDB

Full ADRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADRB1 p.Asn76= Benign/Likely benign ★★ same type
ADRB1 p.Asp382Gly Benign ★★ same type
ADRB1 p.Cys180= Benign ★★ same type
ADRB1 p.Leu105= Benign ★★ same type
ADRB1 p.Ser49Gly Likely benign ★★ same type
ADRB1 p.Val5Ala Benign ★★ same type
ADRB1 p.Val69= Benign ★★ same type
ADRB1 p.Ala227Ser 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/adrb1-p-pro355 (accessed [today's date]).

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