Is RB1 p.Ser347= (c.1041T>A) pathogenic?

RB1 p.Ser347= (c.1041T>A) is classified Likely benign in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-27). Very rare (popmax 0.00168%, amr); Associated with retinoblastoma.

What condition is associated with RB1 p.Ser347= (c.1041T>A)?

RB1 p.Ser347= (c.1041T>A) is associated with retinoblastoma (ClinVar).

How common is RB1 p.Ser347= (c.1041T>A) in the general population?

RB1 p.Ser347= (c.1041T>A) is very rare (popmax 0.00168%, amr) (gnomAD).

How is Retinoblastoma inherited?

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

RB1 p.Ser347=

c.1041T>A · rs1354204219 · VCV1116318

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

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 0.66	GERP 0.5, phastCons 0.37
Overall
CADD	7.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,674 alleles

Overall 6.89e-05% 1/1,451,216 alleles · very rare

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.Ser347=
Coding: c.1041T>A
MANE Select: NM_000321
dbSNP: rs1354204219
Type: single nucleotide variant
Location: chr13:48367595 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 347: an α-helix

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.Ser347Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
RB1 p.Ser347fs Pathogenic ★ same residue
RB1 p.Ser347Tyr 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-ser347 (accessed [today's date]).

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