Is TP53 c.993+257del pathogenic?

TP53 c.993+257del is classified Likely benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Very rare (popmax 8.6e-05%, nfe); Associated with head and neck squamous cell carcinoma.

What condition is associated with TP53 c.993+257del?

TP53 c.993+257del is associated with head and neck squamous cell carcinoma (ClinVar).

How common is TP53 c.993+257del in the general population?

TP53 c.993+257del is very rare (popmax 8.6e-05%, nfe) (gnomAD).

TP53 c.993+257del

rs1373684374 · VCV803306

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.6e-05%, nfe)

Conditions

head and neck squamous cell carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +257	deep intronic (+257 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.19	GERP -2.7, phastCons 0.33
Overall
CADD	7.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.6e-05% European (non-Finnish) · 1/1,162,188 alleles

Overall 0.000253% 4/1,583,734 alleles · very rare exomes 2/1,431,654 · genomes 2/152,080 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00489%	20,469
European (non-Finnish)grpmax	8.6e-05%	1,162,188

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.993+257del
MANE Select: NM_000546
dbSNP: rs1373684374
Type: Deletion
Location: chr17:7673278 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB

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 c.376-160_376-158del Benign/Likely benign ★★ same condition
TP53 c.376-158del Likely benign ★ same condition
TP53 c.376-161_376-158del Likely benign ★ same condition
TP53 p.Arg158Pro Pathogenic ★★★ same condition
TP53 p.Arg175His Pathogenic ★★★ same condition
TP53 p.Arg273His Pathogenic ★★★ same condition
TP53 p.Gly279Glu Pathogenic ★★★ same condition
TP53 p.Lys132Asn 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-c-993-plus-257del (accessed [today's date]).

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