RB1 p.Ser758=
c.2274G>A · rs558114005 · VCV579969
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00673%, eas)
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3 | GERP -3.1 |
| Overall | ||
| CADD | 1.726 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00673%
East Asian · 3/44,572 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00137%
Overall
0.00187%
30/1,606,916 alleles · very rare
exomes 28/1,460,156 · genomes 2/146,760 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00673% | 14,857 |
| South Asian | 0.0055% | 18,184 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,144 |
| Admixed American | 0.0017% | 58,880 |
| European (non-Finnish) | 0.00161% | 62,006 |
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.Ser758=
- Coding
- c.2274G>A
- MANE Select
- NM_000321
- dbSNP
- rs558114005
- Type
- single nucleotide variant
- Location
- chr13:48465060 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 19 PDB
- Residue 758
- an α-helix; the 'pocket; binds t and e1a' region; the 'domain b' region
Similar variants
- RB1 p.Ser758Leu Benign/Likely benign ★★ same residue
- RB1 p.Ser758Ter Pathogenic ★ same residue
- RB1 p.Ser758Pro Uncertain significance ★ ⚠ same residue
- RB1 c.1049+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1049+1G>T Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1049+3A>G Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1050-2A>G Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1128-1G>A 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-ser758 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown