Is ARRB2 p.Ser331Phe (c.992C>T) pathogenic?

ARRB2 p.Ser331Phe (c.992C>T) is classified Uncertain significance in ARRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely pathogenic (0.788); Absent from gnomAD v4.1.

How common is ARRB2 p.Ser331Phe (c.992C>T) in the general population?

ARRB2 p.Ser331Phe (c.992C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARRB2 p.Ser331Phe (c.992C>T)?

AlphaMissense predicts likely pathogenic (score 0.788) — an in-silico prediction, not a clinical call.

ARRB2 p.Ser331Phe

c.992C>T · rs2507730367 · VCV3129846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.788 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.788	likely pathogenic
REVEL	0.324	indeterminate
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, 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

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.Ser331Phe
Coding: c.992C>T
MANE Select: NM_004313
dbSNP: rs2507730367
Type: single nucleotide variant
Location: chr17:4720290 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 83.97 · 1 PDB
Residue 331: 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-ser331phe (accessed [today's date]).

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