Is PLG p.Ser477= (c.1431C>T) pathogenic?

PLG p.Ser477= (c.1431C>T) is classified Benign/Likely benign in PLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-02). Rare (popmax 0.691%, afr); Associated with hypoplasminogenemia.

What condition is associated with PLG p.Ser477= (c.1431C>T)?

PLG p.Ser477= (c.1431C>T) is associated with hypoplasminogenemia, angioedema, hereditary, 4 (ClinVar).

How common is PLG p.Ser477= (c.1431C>T) in the general population?

PLG p.Ser477= (c.1431C>T) is rare (popmax 0.691%, afr) (gnomAD).

How is Hypoplasminogenemia inherited?

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

PLG p.Ser477=

c.1431C>T · rs4699 · VCV719713

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.691%, afr)

Conditions

hypoplasminogenemia

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 -3.7	GERP -3.2
Overall
CADD	0.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.691% African / African-American · 518/75,002 alleles

Filtering AF 0.641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.622%

Overall 0.0751% 1,211/1,613,272 alleles · rare exomes 857/1,461,010 · genomes 354/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.691%	145
Remaining individualsnot grpmax-eligible	0.0768%	1,301
Admixed American	0.0517%	1,936
European (non-Finnish)	0.0516%	1,940
Finnishnot grpmax-eligible	0.00469%	21,337
East Asian	0.00223%	44,860
South Asian	0.0022%	45,534

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.Ser477=
Coding: c.1431C>T
MANE Select: NM_000301
dbSNP: rs4699
Type: single nucleotide variant
Location: chr6:160731225 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.53 · 49 PDB

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-ser477 (accessed [today's date]).

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