Is RB1 p.Pro357del (c.1067CAC[1]) pathogenic?

RB1 p.Pro357del (c.1067CAC[1]) is classified Uncertain significance in RB1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-13). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Pro357del (c.1067CAC[1])?

RB1 p.Pro357del (c.1067CAC[1]) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Pro357del (c.1067CAC[1]) in the general population?

RB1 p.Pro357del (c.1067CAC[1]) is absent from gnomAD (gnomAD).

RB1 p.Pro357del

c.1067CAC[1] · rs1952726639 · VCV1783135

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RB1
Protein: p.Pro357del
Coding: c.1067CAC[1]
MANE Select: NM_000321
dbSNP: rs1952726639
Type: Microsatellite
Location: chr13:48368544 (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

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

Also linked: retinoblastoma

Similar variants

RB1 p.Pro357Ser Uncertain significance ★★ ⚠ same residue
RB1 p.Pro357Thr Uncertain significance ★★ ⚠ same residue
RB1 p.Pro357Leu Uncertain significance ★ same residue
RB1 p.Arg355fs Pathogenic ★★ same condition
RB1 p.Asn480del Pathogenic ★★ same condition
RB1 p.Gln354fs Pathogenic ★★ same condition
RB1 p.Glu629fs Pathogenic ★★ same condition
RB1 p.Ser230fs 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-pro357del (accessed [today's date]).

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