Is RB1 p.Arg7fs (c.19del) pathogenic?

RB1 p.Arg7fs (c.19del) is classified Pathogenic in RB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). Very rare (popmax 0.00246%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Arg7fs (c.19del)?

RB1 p.Arg7fs (c.19del) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Arg7fs (c.19del) in the general population?

RB1 p.Arg7fs (c.19del) is very rare (popmax 0.00246%, sas) (gnomAD).

RB1 p.Arg7fs

c.19del · rs1131690852 · VCV1073217

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00246%, sas)

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 1 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP -2.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% South Asian · 2/81,268 alleles

Filtering AF 0.000409% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000153%

Overall 0.000297% 4/1,347,574 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00246%	40,634
European (non-Finnish)	0.000177%	564,685

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RB1
Protein: p.Arg7fs
Coding: c.19del
MANE Select: NM_000321
dbSNP: rs1131690852
Type: Deletion
Location: chr13:48303926 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 7: 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.Arg7Gln Uncertain significance ★★ ⚠ same residue
RB1 p.Arg7= Benign/Likely benign ★★ same residue
RB1 p.Arg7Gly Uncertain significance ★ ⚠ 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

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-arg7fs (accessed [today's date]).

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