RB1 p.Ser114=
c.342G>A · rs748093967 · VCV237672
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 -3.1 | GERP -3.4 |
| Overall | ||
| CADD | 5.076 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,022 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00124%
20/1,611,650 alleles · very rare
exomes 19/1,459,652 · genomes 1/151,998 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,756 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,200 |
| African / African-American | 0.00134% | 74,852 |
| European (non-Finnish) | 0.0011% | 90,627 |
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.Ser114=
- Coding
- c.342G>A
- MANE Select
- NM_000321
- dbSNP
- rs748093967
- Type
- single nucleotide variant
- Location
- chr13:48342676 (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.Ser114Leu Benign/Likely benign ★★ same residue
- RB1 p.Ser114Ter Pathogenic ★ 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
- RB1 c.1128-2A>G 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-ser114 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown