Is RB1 p.Cys61Leu (c.182_183delinsTG) pathogenic?

RB1 p.Cys61Leu (c.182183delinsTG) is classified Uncertain significance in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Associated with retinoblastoma.

What condition is associated with RB1 p.Cys61Leu (c.182_183delinsTG)?

RB1 p.Cys61Leu (c.182_183delinsTG) is associated with retinoblastoma (ClinVar).

How is Retinoblastoma inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

RB1 p.Cys61Leu

c.182_183delinsTG · VCV4736215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

retinoblastoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
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

Variant & gene context

Gene: RB1
Protein: p.Cys61Leu
Coding: c.182_183delinsTG
MANE Select: NM_000321
Type: Indel
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

retinoblastoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinoblastoma (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Antenatal, Childhood, Infancy
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

RB1 p.Cys61= Likely benign ★★ same residue
RB1 p.Cys61Phe Uncertain significance ★ ⚠ same residue
RB1 p.Cys61Tyr Uncertain significance ★ ⚠ same residue
RB1 c.2325+3_2325+6delinsG Uncertain significance ★★ same condition
RB1 p.Ala14Leu Uncertain significance ★★ same condition
RB1 p.Ala59Pro Uncertain significance ★★ same condition
RB1 p.Lys574Glu Uncertain significance ★★ same condition
RB1 c.1216-17_1216-16delinsTG Benign/Likely benign ★★ 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-cys61leu (accessed [today's date]).

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