Is TP53I3 p.Pro91= (c.273C>T) pathogenic?

TP53I3 p.Pro91= (c.273C>T) is classified Benign in TP53I3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). Low-frequency (popmax 2.55%, afr); Associated with TP53I3-related disorder.

What condition is associated with TP53I3 p.Pro91= (c.273C>T)?

TP53I3 p.Pro91= (c.273C>T) is associated with TP53I3-related disorder (ClinVar).

How common is TP53I3 p.Pro91= (c.273C>T) in the general population?

TP53I3 p.Pro91= (c.273C>T) is low-frequency (popmax 2.55%, afr) (gnomAD).

TP53I3 p.Pro91=

c.273C>T · rs33946528 · VCV3041780

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.55%, afr)

Conditions

TP53I3-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.5	GERP -3.9
Overall
CADD	0.282	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.55% African / African-American · 1,915/75,028 alleles

Filtering AF 2.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.42%

Overall 0.206% 3,332/1,614,122 alleles · low-frequency exomes 2,177/1,461,868 · genomes 1,155/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.55%	39
South Asian	1.29%	77
Remaining individualsnot grpmax-eligible	0.178%	563
Middle Eastern	0.115%	866
Admixed American	0.0866%	1,154
East Asian	0.0111%	8,977
European (non-Finnish)	0.00534%	18,730

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: TP53I3
Protein: p.Pro91=
Coding: c.273C>T
MANE Select: NM_004881
dbSNP: rs33946528
Type: single nucleotide variant
Location: chr2:24083018 (GRCh38)

Full TP53I3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TP53I3-related disorder

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/tp53i3-p-pro91 (accessed [today's date]).

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