Is PLG p.Ser591Pro (c.1771T>C) pathogenic?

PLG p.Ser591Pro (c.1771T>C) is classified Pathogenic in PLG (ClinVar, No assertion criteria, 1 submitter; last evaluated 1993-07-15). AlphaMissense: likely pathogenic (0.9793); Absent from gnomAD v4.1; Associated with dysplasminogenemia.

What condition is associated with PLG p.Ser591Pro (c.1771T>C)?

PLG p.Ser591Pro (c.1771T>C) is associated with dysplasminogenemia (ClinVar).

How common is PLG p.Ser591Pro (c.1771T>C) in the general population?

PLG p.Ser591Pro (c.1771T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLG p.Ser591Pro (c.1771T>C)?

AlphaMissense predicts likely pathogenic (score 0.9793) — an in-silico prediction, not a clinical call.

PLG p.Ser591Pro

c.1771T>C · rs121918029 · VCV13576

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dysplasminogenemia

Computational evidence

Protein change
AlphaMissense	0.9793	likely pathogenic ✓ concordant with ClinVar · top 5% in PLG
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -17.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 50 kb · p 0.011 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLG
Protein: p.Ser591Pro
Coding: c.1771T>C
MANE Select: NM_000301
dbSNP: rs121918029
Type: single nucleotide variant
Location: chr6:160736976 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.53 · 49 PDB
Residue 591: the peptidase s1 domain; a UniProt-annotated variant site (in plgd; risk factor for thrombosis)

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

Disease context

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

Similar variants

PLG p.Gly751Arg Uncertain significance ★★ ⚠ same condition
PLG p.Val374Phe Pathogenic ⚠ same condition
PLG p.Lys330Glu Pathogenic ★★ ⚠ same type
PLG p.Lys38Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
PLG c.2271+5G>A Uncertain significance ★★ same type
PLG c.669-3C>G Uncertain significance ★★ same type
PLG p.Ala216Thr Uncertain significance ★★ ⚠ same type
PLG p.Ala459Val Uncertain significance ★★ ⚠ 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/plg-p-ser591pro (accessed [today's date]).

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