Is CDKN1A p.Arg48Ter (c.142C>T) pathogenic?

CDKN1A p.Arg48Ter (c.142C>T) is classified Pathogenic in CDKN1A (ClinVar, No assertion criteria, 2 submitters). Very rare (popmax 0.0011%, sas); Associated with urinary bladder cancer.

What condition is associated with CDKN1A p.Arg48Ter (c.142C>T)?

CDKN1A p.Arg48Ter (c.142C>T) is associated with urinary bladder cancer (ClinVar).

How common is CDKN1A p.Arg48Ter (c.142C>T) in the general population?

CDKN1A p.Arg48Ter (c.142C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CDKN1A p.Arg48Ter

c.142C>T · rs1407742055 · VCV2582285

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

urinary bladder cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	Δ0.65	donor gain · deltas
Pangolin	Δ0.45	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 1.8, phastCons 0.99
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,612,100 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.000593%	168,562

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKN1A
Protein: p.Arg48Ter
Coding: c.142C>T
MANE Select: NM_000389
dbSNP: rs1407742055
Type: single nucleotide variant
Location: chr6:36684243 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.16 · 13 PDB

Full CDKN1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

urinary bladder cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDKN1A p.Arg48Gln Uncertain significance ★ ⚠ same residue
CDKN1A p.Trp65_Glu66delinsTer Uncertain significance same condition
CDKN1A p.Arg84Gln Likely benign ★★ ⚠ same type
CDKN1A p.Pro4= Benign/Likely benign ★★ same type
CDKN1A p.Ser31= Likely benign ★★ same type
CDKN1A p.Thr80= Likely benign ★★ same type
CDKN1A p.Ala106Val Uncertain significance ★ ⚠ same type
CDKN1A p.Arg20His Uncertain significance ★ ⚠ same type

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/cdkn1a-p-arg48ter (accessed [today's date]).

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