Is RB1 p.Asp479= (c.1437C>T) pathogenic?

RB1 p.Asp479= (c.1437C>T) is classified Uncertain significance in RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). No allele count reported in gnomAD v4.1 (AN 1,589,316); Associated with retinoblastoma.

What condition is associated with RB1 p.Asp479= (c.1437C>T)?

RB1 p.Asp479= (c.1437C>T) is associated with retinoblastoma (ClinVar).

How common is RB1 p.Asp479= (c.1437C>T) in the general population?

RB1 p.Asp479= (c.1437C>T) is no allele count reported in gnomAD v4.1 (AN 1,589,316) (gnomAD).

How is Retinoblastoma inherited?

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

RB1 p.Asp479=

c.1437C>T · rs2138142808 · VCV2114050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,316)

Conditions

retinoblastoma

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
Pangolin	Δ0.27	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Overall
CADD	13.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,316). 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.Asp479=
Coding: c.1437C>T
MANE Select: NM_000321
dbSNP: rs2138142808
Type: single nucleotide variant
Location: chr13:48380180 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 479: the 'pocket; binds t and e1a' region; the 'domain a' region

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.Asp479Gly Uncertain significance ★★ ⚠ same residue
RB1 p.Asp479Asn Uncertain significance ★ ⚠ same residue
RB1 p.Asp479His 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

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-asp479 (accessed [today's date]).

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