Is RB1 p.Pro20Phe (c.58_59delinsTT) pathogenic?

RB1 p.Pro20Phe (c.5859delinsTT) is classified Uncertain significance in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Pro20Phe (c.58_59delinsTT)?

RB1 p.Pro20Phe (c.58_59delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

RB1 p.Pro20Phe

c.58_59delinsTT · VCV3430858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

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 3.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 156 kb · p 9.1e-08 · regional, not allelic
Region caveats
Repeat context	tandem	(GCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Variant & gene context

Gene: RB1
Protein: p.Pro20Phe
Coding: c.58_59delinsTT
MANE Select: NM_000321
Type: Indel
Location: chr13:48303970 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 20: 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.Pro20Ser Uncertain significance ★★ ⚠ same residue
RB1 p.Pro20Thr Uncertain significance ★★ ⚠ same residue
RB1 p.Pro20= Likely benign ★★ same residue
RB1 p.Pro20Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RB1 p.Ala14Leu Uncertain significance ★★ same condition
RB1 p.Ala59Pro Uncertain significance ★★ same condition
RB1 p.Lys574Glu Uncertain significance ★★ same condition
RB1 c.1047_1049+168delinsATCAATAA 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-pro20phe (accessed [today's date]).

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