Is RB1 p.Ser508fs (c.1522dup) pathogenic?

RB1 p.Ser508fs (c.1522dup) is classified Pathogenic in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Ser508fs (c.1522dup)?

RB1 p.Ser508fs (c.1522dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RB1 p.Ser508fs (c.1522dup) in the general population?

RB1 p.Ser508fs (c.1522dup) is no gnomAD frequency available for this variant (gnomAD).

RB1 p.Ser508fs

c.1522dup · rs2542206509 · VCV3231191

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

hereditary neoplastic syndrome

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 17 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.1	GERP 1.6, 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.Ser508fs
Coding: c.1522dup
MANE Select: NM_000321
dbSNP: rs2542206509
Type: Duplication
Location: chr13:48381268 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 508: 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

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

Similar variants

RB1 p.Ser508Phe Uncertain significance ★ ⚠ same residue
RB1 p.Ser508Ala Likely benign ★ same residue
RB1 c.607+2dup Pathogenic ★★ same condition
RB1 p.Asp511fs Pathogenic ★★ same condition
RB1 p.Gln121fs Pathogenic ★★ same condition
RB1 p.Leu797_Arg798insGlnValSerTerProLeu Pathogenic ★★ same condition
RB1 p.Tyr655fs Pathogenic/Likely pathogenic ★★ same condition
RB1 p.Ala16_Ala18dup Uncertain significance ★★ 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-ser508fs (accessed [today's date]).

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