Is RB1 p.Pro892Ser (c.2674C>T) pathogenic?

RB1 p.Pro892Ser (c.2674C>T) is classified Conflicting classifications of pathogenicity in RB1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-19). AlphaMissense: likely benign (0.0877); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Pro892Ser (c.2674C>T)?

RB1 p.Pro892Ser (c.2674C>T) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Pro892Ser (c.2674C>T) in the general population?

RB1 p.Pro892Ser (c.2674C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RB1 p.Pro892Ser (c.2674C>T)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

RB1 p.Pro892Ser

c.2674C>T · rs1949510444 · VCV1794593

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -4.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.21, phastCons 0.88
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 0.0046 · regional, not allelic
Overall
CADD	13.09	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro892Ser
Coding: c.2674C>T
MANE Select: NM_000321
dbSNP: rs1949510444
Type: single nucleotide variant
Location: chr13:48477365 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 892: the 'disordered' region; 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.Pro892Leu Uncertain significance ★★ ⚠ same residue
RB1 p.Pro892Gln 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
RB1 c.1128-2A>G 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-pro892ser (accessed [today's date]).

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