Is TP53 p.Pro82Ser (c.244C>T) pathogenic?

TP53 p.Pro82Ser (c.244C>T) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0711); Very rare (popmax 0.00446%, eas); Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Pro82Ser (c.244C>T)?

TP53 p.Pro82Ser (c.244C>T) is associated with Li-Fraumeni syndrome, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Pro82Ser (c.244C>T) in the general population?

TP53 p.Pro82Ser (c.244C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Li-Fraumeni syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TP53 p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

TP53 p.Pro82Ser

c.244C>T · rs1555526664 · VCV1021579

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Li-Fraumeni syndrome

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -9.62	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 2.5	GERP -0.59, phastCons 0.033
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	9.226	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,870 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,460,732 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.Pro82Ser
Coding: c.244C>T
MANE Select: NM_000546
dbSNP: rs1555526664
Type: single nucleotide variant
Location: chr17:7676125 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 82: a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region; the 'interaction with wwox' region

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

Disease context

Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Li-Fraumeni syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (United Kingdom)

Similar variants

TP53 p.Pro82Leu Likely benign ★★★ ⚠ same residue
TP53 p.Pro82= Benign/Likely benign ★★ same residue
TP53 p.Pro82Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro82Arg Uncertain significance ★ ⚠ same residue
TP53 p.Pro82Thr Likely benign ★ ⚠ same residue
TP53 p.Pro82fs Pathogenic ★ same residue
TP53 p.Pro82_Ala83insThrPro Uncertain significance ★ same residue
TP53 c.375+5G>A 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-pro82ser (accessed [today's date]).

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