Is RB1 p.Asp604= (c.1812T>C) pathogenic?

RB1 p.Asp604= (c.1812T>C) is classified Benign/Likely benign in RB1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-24). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Asp604= (c.1812T>C)?

RB1 p.Asp604= (c.1812T>C) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Asp604= (c.1812T>C) in the general population?

RB1 p.Asp604= (c.1812T>C) is absent from gnomAD v4.1 (gnomAD).

RB1 p.Asp604=

c.1812T>C · rs2138327432 · VCV1583027

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP 0.64, phastCons 0.77
Overall
CADD	7.658	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.Asp604=
Coding: c.1812T>C
MANE Select: NM_000321
dbSNP: rs2138327432
Type: single nucleotide variant
Location: chr13:48453109 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 604: an α-helix; the 'pocket; binds t and e1a' region; the 'spacer' 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.Asp604Asn Uncertain significance ★★ ⚠ same residue
RB1 p.Asp604Gly Uncertain significance ★★ ⚠ same residue
RB1 p.Asp604fs 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-asp604 (accessed [today's date]).

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