Is ARRB2 p.Cys60Ser (c.179G>C) pathogenic?

ARRB2 p.Cys60Ser (c.179G>C) is classified Uncertain significance in ARRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely pathogenic (0.944); Absent from gnomAD v4.1.

How common is ARRB2 p.Cys60Ser (c.179G>C) in the general population?

ARRB2 p.Cys60Ser (c.179G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARRB2 p.Cys60Ser (c.179G>C)?

AlphaMissense predicts likely pathogenic (score 0.944) — an in-silico prediction, not a clinical call.

ARRB2 p.Cys60Ser

c.179G>C · VCV3316167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.944	likely pathogenic
REVEL	0.675	pathogenic-leaning
SaProt	LLR -12.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 10 kb · p 5.2e-12 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARRB2
Protein: p.Cys60Ser
Coding: c.179G>C
MANE Select: NM_004313
Type: single nucleotide variant
Location: chr17:4716430 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 83.97 · 1 PDB

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-cys60ser (accessed [today's date]).

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