Is RBL2 p.Ala263Pro (c.787G>C) pathogenic?

RBL2 p.Ala263Pro (c.787G>C) is classified Uncertain significance in RBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-30). AlphaMissense: likely benign (0.0785); Absent from gnomAD v4.1.

How common is RBL2 p.Ala263Pro (c.787G>C) in the general population?

RBL2 p.Ala263Pro (c.787G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RBL2 p.Ala263Pro (c.787G>C)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

RBL2 p.Ala263Pro

c.787G>C · VCV3373117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.29	GERP -5.4, phastCons 0.001
Regional constraint	o/e 0.84	unconstrained · MANE · 51 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	16.75	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: RBL2
Protein: p.Ala263Pro
Coding: c.787G>C
MANE Select: NM_005611
Type: single nucleotide variant
Location: chr16:53453472 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 2 PDB
Residue 263: a UniProt-annotated variant site (in bruwag)

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

Similar variants

RBL2 p.Pro699Ser Uncertain significance ★★ ⚠ same type
RBL2 p.Pro702Ser Uncertain significance ★★ ⚠ same type
RBL2 p.Ser929Arg Uncertain significance ★★ ⚠ same type
RBL2 p.Thr423Met Uncertain significance ★★ ⚠ same type
RBL2 p.Tyr111Cys Uncertain significance ★★ ⚠ same type
RBL2 p.Arg829Ser Benign ★★ same type
RBL2 p.Arg852= Benign/Likely benign ★★ same type
RBL2 p.Asn549Ile Benign ★★ 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/rbl2-p-ala263pro (accessed [today's date]).

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