Is TP53I3 p.Pro25= (c.75G>C) pathogenic?

TP53I3 p.Pro25= (c.75G>C) is classified Likely benign in TP53I3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-15). Ultra-rare (popmax 0.0426%, afr); Associated with TP53I3-related disorder.

What condition is associated with TP53I3 p.Pro25= (c.75G>C)?

TP53I3 p.Pro25= (c.75G>C) is associated with TP53I3-related disorder (ClinVar).

How common is TP53I3 p.Pro25= (c.75G>C) in the general population?

TP53I3 p.Pro25= (c.75G>C) is ultra-rare (popmax 0.0426%, afr) (gnomAD).

TP53I3 p.Pro25=

c.75G>C · rs34704159 · VCV3036962

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0426%, 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 -9.1	GERP -4
Overall
CADD	0.654	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0426% African / African-American · 32/75,068 alleles

Filtering AF 0.0309% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.027%

Overall 0.0026% 42/1,614,134 alleles · ultra-rare exomes 21/1,461,768 · genomes 21/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0426%	2,346
Admixed American	0.00666%	15,007
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.000169%	590,002

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.Pro25=
Coding: c.75G>C
MANE Select: NM_004881
dbSNP: rs34704159
Type: single nucleotide variant
Location: chr2:24084252 (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-pro25 (accessed [today's date]).

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