Is TP53 p.Pro27Ser (c.79C>T) pathogenic?

TP53 p.Pro27Ser (c.79C>T) is classified Uncertain significance in TP53 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-23). AlphaMissense: likely benign (0.1995); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro27Ser (c.79C>T)?

TP53 p.Pro27Ser (c.79C>T) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Pro27Ser (c.79C>T) in the general population?

TP53 p.Pro27Ser (c.79C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TP53 p.Pro27Ser (c.79C>T)?

AlphaMissense predicts likely benign (score 0.1995) — an in-silico prediction, not a clinical call.

TP53 p.Pro27Ser

c.79C>T · rs922736614 · VCV528271

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1995	likely benign
REVEL	0.623	indeterminate
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.84e-05% 1/1,461,666 alleles · very rare

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.Pro27Ser
Coding: c.79C>T
MANE Select: NM_000546
dbSNP: rs922736614
Type: single nucleotide variant
Location: chr17:7676399 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 27: an α-helix; the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'transcription activation (acidic)' 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: Li-Fraumeni syndrome

Similar variants

TP53 p.Pro27Arg Uncertain significance ★★ ⚠ same residue
TP53 p.Pro27= Likely benign ★★ same residue
TP53 p.Pro27Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro27Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro27Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro27fs Pathogenic ★★ 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-pro27ser (accessed [today's date]).

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