Is TP53I3 p.Pro54Ser (c.160C>T) pathogenic?

TP53I3 p.Pro54Ser (c.160C>T) is classified Uncertain significance in TP53I3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-02). AlphaMissense: ambiguous (0.3641); Very rare (popmax 0.00204%, nfe); Associated with TP53I3-related disorder.

What condition is associated with TP53I3 p.Pro54Ser (c.160C>T)?

TP53I3 p.Pro54Ser (c.160C>T) is associated with TP53I3-related disorder (ClinVar).

How common is TP53I3 p.Pro54Ser (c.160C>T) in the general population?

TP53I3 p.Pro54Ser (c.160C>T) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about TP53I3 p.Pro54Ser (c.160C>T)?

AlphaMissense predicts ambiguous (score 0.3641) — an in-silico prediction, not a clinical call.

TP53I3 p.Pro54Ser

c.160C>T · rs760058149 · VCV2634857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

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
AlphaMissense	0.3641	ambiguous
REVEL	0.229	benign-leaning
SaProt	LLR -12.75	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,744 bp · p 0.047 · regional, not allelic
Overall
CADD	22.5	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 0.00204% European (non-Finnish) · 24/1,179,242 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,612,700 alleles · very rare exomes 22/1,460,522 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	49,135
African / African-American	0.00133%	74,918

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.Pro54Ser
Coding: c.160C>T
MANE Select: NM_004881
dbSNP: rs760058149
Type: single nucleotide variant
Location: chr2:24083131 (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-pro54ser (accessed [today's date]).

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