Is RB1 p.Ser618fs (c.1853_1857del) pathogenic?

RB1 p.Ser618fs (c.18531857del) is classified Pathogenic in RB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-20). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Ser618fs (c.1853_1857del)?

RB1 p.Ser618fs (c.1853_1857del) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Ser618fs (c.1853_1857del) in the general population?

RB1 p.Ser618fs (c.1853_1857del) is no gnomAD frequency available for this variant (gnomAD).

RB1 p.Ser618fs

c.1853_1857del · rs2542364044 · VCV2565235

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 19 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.34	GERP -0.086, phastCons 0.027

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.Ser618fs
Coding: c.1853_1857del
MANE Select: NM_000321
dbSNP: rs2542364044
Type: Deletion
Location: chr13:48456241 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 618: the 'pocket; binds t and e1a' region; the 'spacer' region; 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

Also linked: retinoblastoma

Similar variants

RB1 p.Ser618Leu Uncertain significance ★★ ⚠ same residue
RB1 p.Ser618Ter Pathogenic ★ same residue
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

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-ser618fs (accessed [today's date]).

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