Is RBL2 p.Arg151fs (c.452_453del) pathogenic?

RBL2 p.Arg151fs (c.452453del) is classified Likely pathogenic in RBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Associated with Brunet-Wagner neurodevelopmental syndrome.

What condition is associated with RBL2 p.Arg151fs (c.452_453del)?

RBL2 p.Arg151fs (c.452_453del) is associated with Brunet-Wagner neurodevelopmental syndrome (ClinVar).

RBL2 p.Arg151fs

c.452_453del · VCV4850249

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Brunet-Wagner neurodevelopmental syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.7	GERP -0.94

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: RBL2
Protein: p.Arg151fs
Coding: c.452_453del
MANE Select: NM_005611
Type: Microsatellite
Location: chr16:53442734 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 2 PDB

Full RBL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brunet-Wagner neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBL2 p.Leu533fs Pathogenic ★ same condition
RBL2 p.Pro699Ser Uncertain significance ★★ ⚠ same condition
RBL2 c.3085-2_3086del Pathogenic ★ same condition
RBL2 p.Arg1047Ter Likely pathogenic ★ same condition
RBL2 p.Arg186Ter Likely pathogenic ★ same condition
RBL2 p.Arg192Ter Pathogenic ★ same condition
RBL2 p.His491fs Likely pathogenic ★ same condition
RBL2 p.Tyr301fs Likely pathogenic ★ same condition

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/rbl2-p-arg151fs (accessed [today's date]).

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