Is TP53 p.Pro153= (c.459C>T) pathogenic?

TP53 p.Pro153= (c.459C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0384%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro153= (c.459C>T)?

TP53 p.Pro153= (c.459C>T) is associated with hereditary neoplastic syndrome, colorectal cancer, breast cancer (ClinVar).

How common is TP53 p.Pro153= (c.459C>T) in the general population?

TP53 p.Pro153= (c.459C>T) is ultra-rare (popmax 0.0384%, sas) (gnomAD).

TP53 p.Pro153=

c.459C>T · rs72661116 · VCV230629

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.5	GERP -5.1
Overall
CADD	0.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% South Asian · 35/91,080 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00421% 68/1,614,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0384%	2,602
East Asian	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.0048%	20,836
Finnishnot grpmax-eligible	0.00468%	21,345
Admixed American	0.00333%	30,009
European (non-Finnish)	0.00169%	59,002
African / African-American	0.00133%	75,044

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.Pro153=
Coding: c.459C>T
MANE Select: NM_000546
dbSNP: rs72661116
Type: single nucleotide variant
Location: chr17:7675153 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 153: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; a UniProt-annotated variant site (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 sporadic cancer; somatic mutation); the 'interaction with hipk1' region; 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer breast cancer Li-Fraumeni syndrome

Similar variants

TP53 p.Pro153Leu Uncertain significance ★ ⚠ same residue
TP53 p.Pro153Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro153del Uncertain significance ★★ same residue
TP53 p.Pro153_Thr155del Likely pathogenic ★ same residue
TP53 p.Pro153fs Pathogenic ★ same residue
TP53 p.Pro153Ala Uncertain significance ⚠ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A 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-pro153 (accessed [today's date]).

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