Is TP53 p.Pro36= (c.108G>A) pathogenic?

TP53 p.Pro36= (c.108G>A) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 24 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.34%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro36= (c.108G>A)?

TP53 p.Pro36= (c.108G>A) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is TP53 p.Pro36= (c.108G>A) in the general population?

TP53 p.Pro36= (c.108G>A) is low-frequency (popmax 2.34%, amr) (gnomAD).

TP53 p.Pro36=

c.108G>A · rs1800370 · VCV132708

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 24 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.34%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.5	GERP -3.7
Overall
CADD	9.811	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.34% Admixed American · 1,404/59,994 alleles

Filtering AF 2.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 1.31% 21,147/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.34%	43
Amishnot grpmax-eligible	2.3%	43
European (non-Finnish)	1.44%	70
Middle Eastern	1.32%	76
Remaining individualsnot grpmax-eligible	1.19%	84
South Asian	1.05%	95
Ashkenazi Jewishnot grpmax-eligible	0.676%	148
African / African-American	0.563%	178
Finnishnot grpmax-eligible	0.412%	242
East Asian	0.234%	427

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.Pro36=
Coding: c.108G>A
MANE Select: NM_000546
dbSNP: rs1800370
Type: single nucleotide variant
Location: chr17:7676261 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 36: an α-helix; the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'transcription activation (acidic)' region; a UniProt-annotated variant site (in a sporadic cancer; somatic mutation)

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 Li-Fraumeni syndrome

Similar variants

TP53 p.Pro36Gln Benign ★★★ same residue
TP53 p.Pro36Ser Uncertain significance ★★ ⚠ same residue
TP53 p.Pro36Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro36fs 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-pro36 (accessed [today's date]).

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