Is TP53 p.Arg273Ser (c.817C>A) pathogenic?

TP53 p.Arg273Ser (c.817C>A) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-24). AlphaMissense: likely pathogenic (0.9993); No allele count reported in gnomAD v4.1 (AN 1,613,924); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Arg273Ser (c.817C>A)?

TP53 p.Arg273Ser (c.817C>A) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Arg273Ser (c.817C>A) in the general population?

TP53 p.Arg273Ser (c.817C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,924) (gnomAD).

What do computational predictors say about TP53 p.Arg273Ser (c.817C>A)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

TP53 p.Arg273Ser

c.817C>A · rs121913343 · VCV376656

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,924)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in TP53
REVEL	0.906	moderately pathogenic-leaning
SaProt	LLR -14.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	25.3	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

No allele count reported in gnomAD v4.1 (AN 1,613,924). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TP53
Protein: p.Arg273Ser
Coding: c.817C>A
MANE Select: NM_000546
dbSNP: rs121913343
Type: single nucleotide variant
Location: chr17:7673803 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 273: a DNA-binding region; the 'interaction with axin1' region; a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation; abolishes sequence-specific dna binding; does not induce snai1 degradation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a familial cancer not matching lfs; germline mutation and in sporadic cancers; somatic mutation); the 'interaction with e4f1' region; the 'interaction with dna' region; a β-strand; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' 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.Arg273His Pathogenic ★★★ same residue
TP53 p.Arg273Cys Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg273Gly Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg273Leu Pathogenic ★★ same residue
TP53 p.Arg273Pro Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg273= Conflicting classifications of pathogenicity ★ same residue
TP53 p.Arg273fs Pathogenic ★ same residue
TP53 p.Arg273_Ala276delinsHisThr Uncertain significance ★ same residue

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-arg273ser (accessed [today's date]).

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