Is RB1 p.Phe482fs (c.1445_1446del) pathogenic?

RB1 p.Phe482fs (c.14451446del) is classified Pathogenic in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-19). Absent from gnomAD; Associated with retinoblastoma.

What condition is associated with RB1 p.Phe482fs (c.1445_1446del)?

RB1 p.Phe482fs (c.1445_1446del) is associated with retinoblastoma (ClinVar).

How common is RB1 p.Phe482fs (c.1445_1446del) in the general population?

RB1 p.Phe482fs (c.1445_1446del) is absent from gnomAD (gnomAD).

How is Retinoblastoma inherited?

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

RB1 p.Phe482fs

c.1445_1446del · rs1566199059 · VCV576526

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

retinoblastoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 16 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.1	GERP -2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Phe482fs
Coding: c.1445_1446del
MANE Select: NM_000321
dbSNP: rs1566199059
Type: Deletion
Location: chr13:48380185 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 482: an α-helix; the 'pocket; binds t and e1a' region; the 'domain a' region

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 c.2212-1_2214del Pathogenic ★★ same condition
RB1 c.2326-1del Pathogenic ★★ same condition
RB1 c.2520+1del Pathogenic ★★ same condition
RB1 c.2520+3_2520+6del Pathogenic/Likely pathogenic ★★ same condition
RB1 c.607+1del Pathogenic/Likely pathogenic ★★ same condition
RB1 c.610del Pathogenic ★★ same condition
RB1 c.710_718+5del Likely pathogenic ★★ same condition
RB1 c.-206_-189del 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-phe482fs (accessed [today's date]).

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