Is RB1 p.Pro24Gln (c.71C>A) pathogenic?

RB1 p.Pro24Gln (c.71C>A) is classified Uncertain significance in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.1093); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Pro24Gln (c.71C>A)?

RB1 p.Pro24Gln (c.71C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RB1 p.Pro24Gln (c.71C>A) in the general population?

RB1 p.Pro24Gln (c.71C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RB1 p.Pro24Gln (c.71C>A)?

AlphaMissense predicts likely benign (score 0.1093) — an in-silico prediction, not a clinical call.

RB1 p.Pro24Gln

c.71C>A · rs1285455572 · VCV1757644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1093 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,499,310)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1093	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP 1.1, phastCons 0.65
Regional constraint	o/e 0.81	unconstrained · MANE · 156 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	12.5	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

No allele count reported in gnomAD v4.1 (AN 1,499,310). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RB1
Protein: p.Pro24Gln
Coding: c.71C>A
MANE Select: NM_000321
dbSNP: rs1285455572
Type: single nucleotide variant
Location: chr13:48303983 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 24: the 'disordered' region

Full RB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RB1 p.Pro24Leu Uncertain significance ★★ ⚠ same residue
RB1 p.Pro24= Likely benign ★★ same residue
RB1 p.Pro24Ser Uncertain significance ★ ⚠ same residue
RB1 c.1049+1G>A Pathogenic/Likely pathogenic ★★ same condition
RB1 c.1049+1G>T Pathogenic/Likely pathogenic ★★ same condition
RB1 c.1049+3A>G Pathogenic/Likely pathogenic ★★ same condition
RB1 c.1050-2A>G Pathogenic/Likely pathogenic ★★ same condition
RB1 c.1128-2A>G 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/rb1-p-pro24gln (accessed [today's date]).

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