RB1 p.Val714fs
c.2139dup · VCV4759394
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
hereditary 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 21 of 27 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 0.98, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- RB1
- Protein
- p.Val714fs
- Coding
- c.2139dup
- MANE Select
- NM_000321
- Type
- Duplication
- Location
- chr13:48463760 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 19 PDB
- Residue 714
- an α-helix; the 'pocket; binds t and e1a' region; the 'domain b' region
Disease context
hereditary 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.Leu506fs Pathogenic ★ same condition
- RB1 p.Lys122fs Likely pathogenic ★ same condition
- RB1 p.Ser807fs Pathogenic ★ same condition
- RB1 c.1421+26dup Likely benign ★ same condition
- RB1 c.1128-1G>A Pathogenic ★★ same condition
- RB1 c.1215+1G>A Pathogenic ★★ same condition
- RB1 c.1960+1G>T Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.2211+2T>C 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-val714fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown