Is TP53 p.Pro301= (c.903A>G) pathogenic?

TP53 p.Pro301= (c.903A>G) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-16). Rare (popmax 0.172%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro301= (c.903A>G)?

TP53 p.Pro301= (c.903A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is TP53 p.Pro301= (c.903A>G) in the general population?

TP53 p.Pro301= (c.903A>G) is rare (popmax 0.172%, sas) (gnomAD).

TP53 p.Pro301=

c.903A>G · rs72661120 · VCV184179

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, 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 -1.8	GERP -4.6
Overall
CADD	3.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% South Asian · 157/91,086 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.142%

Overall 0.0108% 174/1,614,162 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.172%	580
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0112%	8,930
African / African-American	0.00266%	37,530
European (non-Finnish)	0.000593%	168,575

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.Pro301=
Coding: c.903A>G
MANE Select: NM_000546
dbSNP: rs72661120
Type: single nucleotide variant
Location: chr17:7673717 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 301: a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'disordered' region; the 'interaction with carm1' region; the 'interaction with ccar2' region; the 'interaction with hipk1' 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: hereditary breast ovarian cancer syndrome breast cancer hereditary breast carcinoma Li-Fraumeni syndrome

Similar variants

TP53 p.Pro301Ala Uncertain significance ★ ⚠ same residue
TP53 p.Pro301Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro301Ser Uncertain significance ★ ⚠ same residue
TP53 p.Pro301fs Pathogenic ★★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ same condition
TP53 c.97-1G>A Pathogenic ★★★ same condition
TP53 p.Ala138Pro Likely 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-pro301 (accessed [today's date]).

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