RB1 p.Ser127=
c.381T>C · rs780321508 · VCV1512892
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000255%, nfe)
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 14.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,178,084 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,610,596 alleles · very rare
exomes 3/1,458,250 · genomes 0/152,346 · joint denominator
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.Ser127=
- Coding
- c.381T>C
- MANE Select
- NM_000321
- dbSNP
- rs780321508
- Type
- single nucleotide variant
- Location
- chr13:48345080 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 19 PDB
Similar variants
- RB1 p.Ser127Asn Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RB1 p.Ser127Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RB1 p.Ser127Ile Likely pathogenic ★ same residue
- RB1 p.Ser127Arg Uncertain significance ★ ⚠ same residue
- RB1 p.Ser127Cys Uncertain significance ★ ⚠ same residue
- RB1 p.Ser127Gly Uncertain significance ★ ⚠ same residue
- RB1 c.1049+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1049+1G>T 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-ser127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown