Is ARRB1 p.Val167Phe (c.499G>T) pathogenic?

ARRB1 p.Val167Phe (c.499G>T) is classified Uncertain significance in ARRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.9204); Very rare (popmax 8.49e-05%, nfe).

How common is ARRB1 p.Val167Phe (c.499G>T) in the general population?

ARRB1 p.Val167Phe (c.499G>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ARRB1 p.Val167Phe (c.499G>T)?

AlphaMissense predicts likely pathogenic (score 0.9204) — an in-silico prediction, not a clinical call.

ARRB1 p.Val167Phe

c.499G>T · VCV4148600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9204 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9204	likely pathogenic
REVEL	0.2	benign-leaning
SaProt	LLR -12.88	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.039, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 77 kb · p 1e-05 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,906 alleles

Overall 6.86e-05% 1/1,458,160 alleles · very rare

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: ARRB1
Protein: p.Val167Phe
Coding: c.499G>T
MANE Select: NM_004041
Type: single nucleotide variant
Location: chr11:75278728 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 82.44 · 35 PDB

Full ARRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARRB1 p.Ala151Thr Uncertain significance ★ ⚠ same type
ARRB1 p.Ala263Thr Uncertain significance ★ ⚠ same type
ARRB1 p.Ala82Ser Uncertain significance ★ ⚠ same type
ARRB1 p.Ala82Thr Uncertain significance ★ ⚠ same type
ARRB1 p.Arg177Ser Uncertain significance ★ ⚠ same type
ARRB1 p.Arg282Gln Uncertain significance ★ ⚠ same type
ARRB1 p.Arg312Cys Uncertain significance ★ ⚠ same type
ARRB1 p.Arg363Gln 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/arrb1-p-val167phe (accessed [today's date]).

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