Is RB1 p.Ser834= (c.2502A>G) pathogenic?

RB1 p.Ser834= (c.2502A>G) is classified Conflicting classifications of pathogenicity in RB1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-22). Very rare (popmax 8.76e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Ser834= (c.2502A>G)?

RB1 p.Ser834= (c.2502A>G) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Ser834= (c.2502A>G) in the general population?

RB1 p.Ser834= (c.2502A>G) is very rare (popmax 8.76e-05%, nfe) (gnomAD).

RB1 p.Ser834=

c.2502A>G · rs1949484214 · VCV1792265

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 8.76e-05%, nfe)

Conditions

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 0.59	GERP -3.4, phastCons 0.92
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.76e-05% European (non-Finnish) · 1/1,141,032 alleles

Overall 6.37e-05% 1/1,569,610 alleles · very rare exomes 1/1,417,326 · genomes 0/152,284 · 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.Ser834=
Coding: c.2502A>G
MANE Select: NM_000321
dbSNP: rs1949484214
Type: single nucleotide variant
Location: chr13:48473372 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 834: a β-strand; the 'interaction with limd1' region; the 'domain c; mediates interaction with e4f1' region

Full RB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinoblastoma

Similar variants

RB1 p.Ser834Ter Pathogenic ★★ same residue
RB1 p.Ser834Leu Uncertain significance ★ ⚠ same residue
RB1 p.Ser834fs 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

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-ser834 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown