Is PLG p.Pro574= (c.1722G>A) pathogenic?

PLG p.Pro574= (c.1722G>A) is classified Likely benign in PLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-28). Very rare (popmax 0.00891%, eas); Associated with hypoplasminogenemia.

What condition is associated with PLG p.Pro574= (c.1722G>A)?

PLG p.Pro574= (c.1722G>A) is associated with hypoplasminogenemia, angioedema, hereditary, 4 (ClinVar).

How common is PLG p.Pro574= (c.1722G>A) in the general population?

PLG p.Pro574= (c.1722G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Hypoplasminogenemia inherited?

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

PLG p.Pro574=

c.1722G>A · rs146030266 · VCV800029

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

hypoplasminogenemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor loss, 40 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -3.3	GERP -2.5
Overall
CADD	2.517	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00372% 60/1,613,858 alleles · very rare exomes 51/1,461,770 · genomes 9/152,088 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.0039%	25,651
Admixed American	0.00333%	29,994
South Asian	0.00329%	30,361
Finnishnot grpmax-eligible	0.00156%	64,000
African / African-American	0.00134%	74,898

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: PLG
Protein: p.Pro574=
Coding: c.1722G>A
MANE Select: NM_000301
dbSNP: rs146030266
Type: single nucleotide variant
Location: chr6:160736927 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.53 · 49 PDB
Residue 574: an α-helix

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

Disease context

hypoplasminogenemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: angioedema, hereditary, 4

For Hypoplasminogenemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PLG p.Lys330Glu Pathogenic ★★ ⚠ same condition
PLG p.Lys38Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
PLG c.669-3C>G Uncertain significance ★★ same condition
PLG p.Ala216Thr Uncertain significance ★★ ⚠ same condition
PLG p.Ala494Glu Uncertain significance ★★ ⚠ same condition
PLG p.Ala507Val Uncertain significance ★★ ⚠ same condition
PLG p.Ala675Val Uncertain significance ★★ ⚠ same condition
PLG p.Arg172Gly Uncertain significance ★★ ⚠ same condition

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/plg-p-pro574 (accessed [today's date]).

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