Is RB1 p.Glu313= (c.939G>A) pathogenic?

RB1 p.Glu313= (c.939G>A) is classified Pathogenic/Likely pathogenic in RB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-20). Absent from gnomAD v4.1; Associated with retinoblastoma.

What condition is associated with RB1 p.Glu313= (c.939G>A)?

RB1 p.Glu313= (c.939G>A) is associated with retinoblastoma (ClinVar).

How common is RB1 p.Glu313= (c.939G>A) in the general population?

RB1 p.Glu313= (c.939G>A) is absent from gnomAD v4.1 (gnomAD).

How is Retinoblastoma inherited?

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

RB1 p.Glu313=

c.939G>A · rs2138116702 · VCV1066671

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinoblastoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.98	donor loss · deltas
Pangolin	Δ0.81	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RB1
Protein: p.Glu313=
Coding: c.939G>A
MANE Select: NM_000321
dbSNP: rs2138116702
Type: single nucleotide variant
Location: chr13:48364971 (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.Glu313Ter Pathogenic ★ same residue
RB1 p.Glu313Gly Uncertain significance ★ ⚠ same residue
RB1 p.Glu313Asp 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
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-glu313 (accessed [today's date]).

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