Is PLG p.Phe314= (c.942C>T) pathogenic?

PLG p.Phe314= (c.942C>T) is classified Benign in PLG (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 44.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with angioedema, hereditary, 4.

What condition is associated with PLG p.Phe314= (c.942C>T)?

PLG p.Phe314= (c.942C>T) is associated with angioedema, hereditary, 4, hypoplasminogenemia (ClinVar).

PLG p.Phe314=

Q: How common is PLG p.Phe314= (c.942C>T) in the general population?

PLG p.Phe314= (c.942C>T) is common (popmax 44.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.942C>T · rs1130656 · VCV1174797

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 44.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

angioedema, hereditary, 4

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 -3.8	GERP -3.5
Overall
CADD	0.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 44.1% East Asian · 19,790/44,840 alleles

Filtering AF 43.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.4%

Overall 39.6% 636,325/1,608,592 alleles · common exomes 582,228/1,456,598 · genomes 54,097/151,994 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	50.7%	2
East Asiangrpmax	44.1%	2
Ashkenazi Jewishnot grpmax-eligible	41.2%	2
South Asian	41.1%	2
European (non-Finnish)	41%	2
Remaining individualsnot grpmax-eligible	39.3%	3
Finnishnot grpmax-eligible	34.4%	3
Middle Eastern	31.9%	3
Admixed American	29%	3
African / African-American	25.3%	4

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe314=
Coding: c.942C>T
MANE Select: NM_000301
dbSNP: rs1130656
Type: single nucleotide variant
Location: chr6:160718448 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.53 · 49 PDB
Residue 314: the kringle 3 domain

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

Disease context

angioedema, hereditary, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypoplasminogenemia

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-phe314 (accessed [today's date]).

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