Is RB1 p.Ala16= (c.48C>T) pathogenic?

RB1 p.Ala16= (c.48C>T) is classified Benign/Likely benign in RB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-23). No allele count reported in gnomAD v4.1 (AN 1,509,290); Associated with retinoblastoma.

What condition is associated with RB1 p.Ala16= (c.48C>T)?

RB1 p.Ala16= (c.48C>T) is associated with retinoblastoma, hereditary neoplastic syndrome (ClinVar).

How common is RB1 p.Ala16= (c.48C>T) in the general population?

RB1 p.Ala16= (c.48C>T) is no allele count reported in gnomAD v4.1 (AN 1,509,290) (gnomAD).

How is Retinoblastoma inherited?

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

RB1 p.Ala16=

c.48C>T · rs2138027367 · VCV1743946

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,509,290)

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
Constraint at this position
Conservation	phyloP -1.4	GERP -2.6
Overall
CADD	6.726	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,509,290). 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.Ala16=
Coding: c.48C>T
MANE Select: NM_000321
dbSNP: rs2138027367
Type: single nucleotide variant
Location: chr13:48303960 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 19 PDB
Residue 16: the 'disordered' 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

Also linked: hereditary neoplastic syndrome

For Retinoblastoma (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Antenatal, Childhood, Infancy
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

RB1 p.Ala16fs Pathogenic ★★ same residue
RB1 p.Ala16_Ala18dup Uncertain significance ★★ same residue
RB1 p.Ala16_Ala18del Benign/Likely benign ★★ 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-ala16 (accessed [today's date]).

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