Is TP53 p.Gln375fs (c.1125del) pathogenic?

TP53 p.Gln375fs (c.1125del) is classified Pathogenic in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-03-23). Absent from gnomAD.

How common is TP53 p.Gln375fs (c.1125del) in the general population?

TP53 p.Gln375fs (c.1125del) is absent from gnomAD (gnomAD).

TP53 p.Gln375fs

c.1125del · rs730882017 · VCV182956

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

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	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 0.23, phastCons 1

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.Gln375fs
Coding: c.1125del
MANE Select: NM_000546
dbSNP: rs730882017
Type: Deletion
Location: chr17:7669666 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 375: the 'interaction with carm1' region; an α-helix; the 'disordered' region; the 'basic (repression of dna-binding)' region; the 'interaction with morn3' region

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

Similar variants

TP53 p.Gln375Ter Uncertain significance ★★ same residue
TP53 p.Gln375= Benign/Likely benign ★★ same residue
TP53 p.Gln375His Uncertain significance ★ ⚠ same residue
TP53 p.Gln375Lys Likely benign ★ same residue
TP53 c.993+1del Likely pathogenic ★★★ same type
TP53 p.Ala161_Tyr163delinsAsp Likely pathogenic ★★★ same type
TP53 p.Arg213fs Pathogenic ★★★ same type
TP53 p.Leu252_Ile254del Pathogenic ★★★ 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/tp53-p-gln375fs (accessed [today's date]).

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