Is PLAU p.Pro54= (c.162A>G) pathogenic?

PLAU p.Pro54= (c.162A>G) is classified Benign/Likely benign in PLAU (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-03-01). Rare (popmax 0.344%, nfe); Associated with Quebec platelet disorder.

What condition is associated with PLAU p.Pro54= (c.162A>G)?

PLAU p.Pro54= (c.162A>G) is associated with Quebec platelet disorder (ClinVar).

How common is PLAU p.Pro54= (c.162A>G) in the general population?

PLAU p.Pro54= (c.162A>G) is rare (popmax 0.344%, nfe) (gnomAD).

How is Quebec platelet disorder inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PLAU p.Pro54=

c.162A>G · rs142059320 · VCV300743

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.344%, nfe)

Conditions

Quebec platelet disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -3.8, phastCons 0.001
Overall
CADD	10.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.344% European (non-Finnish) · 4,063/1,180,020 alleles

Filtering AF 0.335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.332%

Overall 0.274% 4,419/1,613,946 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.344%	290
Remaining individualsnot grpmax-eligible	0.202%	496
Admixed American	0.132%	760
South Asian	0.117%	851
Middle Eastern	0.066%	1,514
African / African-American	0.0333%	3,002
Finnishnot grpmax-eligible	0.0204%	4,908
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,886

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: PLAU
Protein: p.Pro54=
Coding: c.162A>G
MANE Select: NM_002658
dbSNP: rs142059320
Type: single nucleotide variant
Location: chr10:73912291 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 156 PDB
Residue 54: a disulfide bond; the egf-like domain; the 'binds urokinase plasminogen activator surface receptor' region

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

Disease context

Quebec platelet disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Quebec platelet disorder (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Specific population)

Similar variants

PLAU c.-25C>T Benign ★★ same condition
PLAU p.Gly37= Benign/Likely benign ★★ ⚠ same condition
PLAU p.Lys231Gln Benign ★★ same condition
PLAU p.Arg79Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
PLAU c.369-87G>A Benign ★★ same type
PLAU c.*20G>A Uncertain significance ★ same type
PLAU p.Gly374Val Uncertain significance ★ ⚠ same type
PLAU c.58-124A>T Likely benign ★ same type

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/plau-p-pro54 (accessed [today's date]).

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