Is ARRB2 p.Arg283Trp (c.847C>T) pathogenic?

ARRB2 p.Arg283Trp (c.847C>T) is classified Uncertain significance in ARRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely pathogenic (0.7849); Very rare (popmax 0.00534%, afr).

How common is ARRB2 p.Arg283Trp (c.847C>T) in the general population?

ARRB2 p.Arg283Trp (c.847C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ARRB2 p.Arg283Trp (c.847C>T)?

AlphaMissense predicts likely pathogenic (score 0.7849) — an in-silico prediction, not a clinical call.

ARRB2 p.Arg283Trp

c.847C>T · rs370304415 · VCV2338069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7849	likely pathogenic
REVEL	0.565	indeterminate
SaProt	LLR -15.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.81, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 10 kb · p 5.2e-12 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00534% African / African-American · 4/74,916 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00347% 56/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,729
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.00415%	24,082

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: ARRB2
Protein: p.Arg283Trp
Coding: c.847C>T
MANE Select: NM_004313
dbSNP: rs370304415
Type: single nucleotide variant
Location: chr17:4719350 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 83.97 · 1 PDB
Residue 283: the 'interaction with traf6' region

Full ARRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARRB2 p.Ile82= Benign ★★ same type
ARRB2 p.Leu288= Benign ★★ same type
ARRB2 p.Ala362Thr Uncertain significance ★ ⚠ same type
ARRB2 p.Arg100Cys Uncertain significance ★ ⚠ same type
ARRB2 p.Arg148Gln Uncertain significance ★ ⚠ same type
ARRB2 p.Arg189Cys Uncertain significance ★ ⚠ same type
ARRB2 p.Arg196Gln Uncertain significance ★ ⚠ same type
ARRB2 p.Arg26Gln 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/arrb2-p-arg283trp (accessed [today's date]).

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