Is PLG p.Pro143Arg (c.428C>G) pathogenic?

PLG p.Pro143Arg (c.428C>G) is classified Uncertain significance in PLG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely benign (0.1393); Absent from gnomAD v4.1.

How common is PLG p.Pro143Arg (c.428C>G) in the general population?

PLG p.Pro143Arg (c.428C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLG p.Pro143Arg (c.428C>G)?

AlphaMissense predicts likely benign (score 0.1393) — an in-silico prediction, not a clinical call.

PLG p.Pro143Arg

c.428C>G · rs756944864 · VCV1961313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1393 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1393	likely benign
REVEL	0.511	indeterminate
SaProt	LLR -13.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 50 kb · p 0.011 · regional, not allelic
Overall
CADD	25.6	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.Pro143Arg
Coding: c.428C>G
MANE Select: NM_000301
dbSNP: rs756944864
Type: single nucleotide variant
Location: chr6:160713006 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.53 · 49 PDB
Residue 143: a turn; the 'disordered' region; the kringle 1 domain

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

Similar variants

PLG p.Pro143Ser Uncertain significance ★ ⚠ same residue
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
PLG p.Ala494Glu 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-pro143arg (accessed [today's date]).

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