Is TP53 p.Arg209fs (c.626_627del) pathogenic?

TP53 p.Arg209fs (c.626627del) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-05-24). Very rare (popmax 8.47e-05%, nfe); Associated with TP53-related disorder.

What condition is associated with TP53 p.Arg209fs (c.626_627del)?

TP53 p.Arg209fs (c.626_627del) is associated with TP53-related disorder, hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Arg209fs (c.626_627del) in the general population?

TP53 p.Arg209fs (c.626_627del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TP53 p.Arg209fs

c.626_627del · rs1057517840 · VCV372539

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

TP53-related disorder

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 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.34	GERP -3.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,134 alleles · very rare exomes 1/1,461,890 · genomes 0/152,244 · joint denominator

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: TP53
Protein: p.Arg209fs
Coding: c.626_627del
MANE Select: NM_000546
dbSNP: rs1057517840
Type: Deletion
Location: chr17:7674904 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 209: a DNA-binding region; the 'interaction with axin1' region; a turn; the 'interaction with ccar2' region; the 'interaction with hipk1' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'required for interaction with znf385a' region; the 'required for interaction with fbxo42' region

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

Disease context

TP53-related disorder

Also linked: hereditary neoplastic syndrome Li-Fraumeni syndrome ovarian neoplasm

Similar variants

TP53 p.Arg209Lys Likely benign ★★★ same residue
TP53 p.Arg209Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Arg209Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Arg209= Likely benign ★ same residue
TP53 c.993+1del Likely pathogenic ★★★ same condition
TP53 p.Ala161_Tyr163delinsAsp Likely pathogenic ★★★ same condition
TP53 p.Arg213fs Pathogenic ★★★ same condition
TP53 p.Leu252_Ile254del 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-arg209fs (accessed [today's date]).

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