RB1 p.Asn519fs
c.1556dup · VCV4721537
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
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 17 of 27 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6.7 | GERP 1.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- RB1
- Protein
- p.Asn519fs
- Coding
- c.1556dup
- MANE Select
- NM_000321
- Type
- Duplication
- Location
- chr13:48381302 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 19 PDB
- Residue 519
- an α-helix; the 'pocket; binds t and e1a' region; the 'domain a' region
Disease context
retinoblastoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Retinoblastoma (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- Antenatal, Childhood, Infancy
- Prevalence
- <1 / 1 000 000 (Europe)
Similar variants
- RB1 p.Asn519_Asn522del Uncertain significance ★ same residue
- RB1 c.607+2dup Pathogenic ★★ same condition
- RB1 p.Ala22fs Pathogenic ★★ same condition
- RB1 p.Asn133Ter Pathogenic ★★ same condition
- RB1 p.Asp511fs Pathogenic ★★ same condition
- RB1 p.Cys590fs Pathogenic ★★ same condition
- RB1 p.Gln121fs Pathogenic ★★ same condition
- RB1 p.Glu97fs 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-asn519fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown