Is TP53 p.Cys238fs (c.713dup) pathogenic?

TP53 p.Cys238fs (c.713dup) is classified Pathogenic in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD; Associated with head and neck squamous cell carcinoma.

What condition is associated with TP53 p.Cys238fs (c.713dup)?

TP53 p.Cys238fs (c.713dup) is associated with head and neck squamous cell carcinoma (ClinVar).

How common is TP53 p.Cys238fs (c.713dup) in the general population?

TP53 p.Cys238fs (c.713dup) is absent from gnomAD (gnomAD).

TP53 p.Cys238fs

c.713dup · rs1597365075 · VCV803307

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

head and neck squamous cell carcinoma

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 7 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.85	GERP -4.4, phastCons 0.98

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.Cys238fs
Coding: c.713dup
MANE Select: NM_000546
dbSNP: rs1597365075
Type: Duplication
Location: chr17:7674249 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 238: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; a binding site; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in a familial cancer not matching lfs; germline mutation and in sporadic cancers; somatic mutation)

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

Disease context

head and neck squamous cell carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 p.Cys238Arg Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys238Gly Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys238Phe Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys238Ser Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys238Trp Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys238Tyr Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys238_Met243delinsLeu Pathogenic ★ same residue
TP53 p.Cys238Ter Pathogenic ★ same residue

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-cys238fs (accessed [today's date]).

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