Is RB1 p.Cys61Ser (c.182G>C) pathogenic?

RB1 p.Cys61Ser (c.182G>C) is classified Uncertain significance in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-03). AlphaMissense: likely pathogenic (0.7338); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Cys61Ser (c.182G>C)?

RB1 p.Cys61Ser (c.182G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RB1 p.Cys61Ser (c.182G>C) in the general population?

RB1 p.Cys61Ser (c.182G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RB1 p.Cys61Ser (c.182G>C)?

AlphaMissense predicts likely pathogenic (score 0.7338) — an in-silico prediction, not a clinical call.

RB1 p.Cys61Ser

c.182G>C · rs1593414390 · VCV3231202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7338	likely pathogenic
REVEL	0.771	pathogenic-leaning
SaProt	LLR -9.05	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 156 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	22.0	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: RB1
Protein: p.Cys61Ser
Coding: c.182G>C
MANE Select: NM_000321
dbSNP: rs1593414390
Type: single nucleotide variant
Location: chr13:48307324 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 61: an α-helix

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.Cys61= Likely benign ★★ same residue
RB1 p.Cys61Arg Uncertain significance ★ ⚠ same residue
RB1 p.Cys61Phe Uncertain significance ★ ⚠ same residue
RB1 p.Cys61Tyr 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

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-cys61ser (accessed [today's date]).

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