Is RB1 p.Asp718= (c.2154C>T) pathogenic?

RB1 p.Asp718= (c.2154C>T) is classified Likely benign in RB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-23). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RB1 p.Asp718= (c.2154C>T)?

RB1 p.Asp718= (c.2154C>T) is associated with hereditary neoplastic syndrome, retinoblastoma (ClinVar).

How common is RB1 p.Asp718= (c.2154C>T) in the general population?

RB1 p.Asp718= (c.2154C>T) is absent from gnomAD v4.1 (gnomAD).

RB1 p.Asp718=

c.2154C>T · rs1949419727 · VCV1613816

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,458)

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 -0.34	GERP -2, phastCons 0.11
Overall
CADD	6.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,458). 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.Asp718=
Coding: c.2154C>T
MANE Select: NM_000321
dbSNP: rs1949419727
Type: single nucleotide variant
Location: chr13:48463778 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 718: the 'pocket; binds t and e1a' region; the 'domain b' 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.Asp718Glu Uncertain significance ★★ ⚠ same residue
RB1 p.Asp718His Uncertain significance ★ ⚠ same residue
RB1 p.Asp718fs 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-asp718 (accessed [today's date]).

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