Is RB1 p.Ser230= (c.690A>T) pathogenic?

RB1 p.Ser230= (c.690A>T) is classified Likely benign in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). Very rare (popmax 0.0011%, sas); Associated with retinoblastoma.

What condition is associated with RB1 p.Ser230= (c.690A>T)?

RB1 p.Ser230= (c.690A>T) is associated with retinoblastoma (ClinVar).

How common is RB1 p.Ser230= (c.690A>T) in the general population?

RB1 p.Ser230= (c.690A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Retinoblastoma inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

RB1 p.Ser230=

c.690A>T · rs2138107923 · VCV1567660

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

retinoblastoma

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 4.1	GERP 1.3, phastCons 1
Overall
CADD	9.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,026 alleles

Overall 6.2e-05% 1/1,612,252 alleles · very rare exomes 1/1,460,588 · genomes 0/151,664 · 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.Ser230=
Coding: c.690A>T
MANE Select: NM_000321
dbSNP: rs2138107923
Type: single nucleotide variant
Location: chr13:48360099 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB

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

Disease context

retinoblastoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinoblastoma (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Antenatal, Childhood, Infancy
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

RB1 p.Ser230Leu Uncertain significance ★★ ⚠ same residue
RB1 p.Ser230Ter Pathogenic ★ same residue
RB1 p.Ser230Ala Uncertain significance ★ ⚠ same residue
RB1 p.Ser230fs Pathogenic/Likely 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

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-ser230 (accessed [today's date]).

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