Is TP53RK p.Pro15Ser (c.43C>T) pathogenic?

TP53RK p.Pro15Ser (c.43C>T) is classified Uncertain significance in TP53RK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely benign (0.082); Ultra-rare (popmax 0.0182%, sas); Associated with Galloway-Mowat syndrome 4.

What condition is associated with TP53RK p.Pro15Ser (c.43C>T)?

TP53RK p.Pro15Ser (c.43C>T) is associated with Galloway-Mowat syndrome 4 (ClinVar).

How common is TP53RK p.Pro15Ser (c.43C>T) in the general population?

TP53RK p.Pro15Ser (c.43C>T) is ultra-rare (popmax 0.0182%, sas) (gnomAD).

What do computational predictors say about TP53RK p.Pro15Ser (c.43C>T)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

TP53RK p.Pro15Ser

c.43C>T · VCV3587312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Galloway-Mowat syndrome 4

⚠ 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	0.082	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.011	GERP 0.56
Regional constraint	o/e 1.03	unconstrained · MANE · 2,658 bp · p 0.55 · regional, not allelic
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0182% South Asian · 16/87,822 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00929%

Overall 0.00114% 18/1,577,400 alleles · ultra-rare exomes 18/1,425,022 · genomes 0/152,378 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0182%	5,489
Remaining individualsnot grpmax-eligible	0.00326%	30,665

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: TP53RK
Protein: p.Pro15Ser
Coding: c.43C>T
MANE Select: NM_033550
Type: single nucleotide variant
Location: chr20:46689372 (GRCh38)

Full TP53RK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Galloway-Mowat syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/tp53rk-p-pro15ser (accessed [today's date]).

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