Is TP53 p.Ala83fs (c.242_245dup) pathogenic?

TP53 p.Ala83fs (c.242245dup) is classified Pathogenic in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). Absent from gnomAD; Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Ala83fs (c.242_245dup)?

TP53 p.Ala83fs (c.242_245dup) is associated with Li-Fraumeni syndrome 1 (ClinVar).

How common is TP53 p.Ala83fs (c.242_245dup) in the general population?

TP53 p.Ala83fs (c.242_245dup) is absent from gnomAD (gnomAD).

TP53 p.Ala83fs

c.242_245dup · rs2543630848 · VCV3148502

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Li-Fraumeni syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -3.7

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: TP53
Protein: p.Ala83fs
Coding: c.242_245dup
MANE Select: NM_000546
dbSNP: rs2543630848
Type: Duplication
Location: chr17:7676123 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 83: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region; the 'interaction with wwox' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Li-Fraumeni syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 c.375+1dup Pathogenic/Likely pathogenic ★★ same condition
TP53 p.Asp228Ter Pathogenic ★★ same condition
TP53 p.Cys124fs Pathogenic ★★ same condition
TP53 c.376-21_376-20dup Benign/Likely benign ★★ same condition
TP53 p.Ala83= Benign/Likely benign ★★ same residue
TP53 p.Ala83Val Benign/Likely benign ★★ same residue
TP53 c.375_375+1dup Likely pathogenic ★ same condition
TP53 p.Arg306fs 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/tp53-p-ala83fs (accessed [today's date]).

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