Is TP53 p.Pro318Ser (c.952C>T) pathogenic?

TP53 p.Pro318Ser (c.952C>T) is classified Benign in TP53 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0772); Absent from gnomAD v4.1; Associated with acute myeloid leukemia.

What condition is associated with TP53 p.Pro318Ser (c.952C>T)?

TP53 p.Pro318Ser (c.952C>T) is associated with acute myeloid leukemia (ClinVar).

How common is TP53 p.Pro318Ser (c.952C>T) in the general population?

TP53 p.Pro318Ser (c.952C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Pro318Ser (c.952C>T)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

TP53 p.Pro318Ser

c.952C>T · rs2151011743 · VCV2575170

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP 1.2, phastCons 0.02
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	16.74	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP53
Protein: p.Pro318Ser
Coding: c.952C>T
MANE Select: NM_000546
dbSNP: rs2151011743
Type: single nucleotide variant
Location: chr17:7673576 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 318: a UniProt-annotated variant site (in sporadic cancers; 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

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 p.Pro318= Benign/Likely benign ★★ same residue
TP53 p.Pro318Arg Uncertain significance ★ ⚠ same residue
TP53 p.Pro318Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ile254Thr Pathogenic ★★★ same condition
TP53 p.Pro72Arg Benign ★★★ same condition
TP53 p.Arg267Pro Pathogenic ★★ same condition
TP53 p.Arg280Thr Pathogenic/Likely pathogenic ★★ same condition
TP53 p.Cys275Tyr Pathogenic/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-pro318ser (accessed [today's date]).

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