Is SERPINE1 p.Ala119= (c.357G>A) pathogenic?

SERPINE1 p.Ala119= (c.357G>A) is classified Benign/Likely benign in SERPINE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.418%, sas); Associated with congenital plasminogen activator inhibitor type 1 deficiency.

What condition is associated with SERPINE1 p.Ala119= (c.357G>A)?

SERPINE1 p.Ala119= (c.357G>A) is associated with congenital plasminogen activator inhibitor type 1 deficiency (ClinVar).

How common is SERPINE1 p.Ala119= (c.357G>A) in the general population?

SERPINE1 p.Ala119= (c.357G>A) is rare (popmax 0.418%, sas) (gnomAD).

SERPINE1 p.Ala119=

Q: How is Congenital plasminogen activator inhibitor type 1 deficiency inherited?

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

c.357G>A · rs6091 · VCV717078

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.418%, sas)

Conditions

congenital plasminogen activator inhibitor type 1 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 0.42, phastCons 1
Overall
CADD	13.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.418% South Asian · 381/91,082 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.37%

Overall 0.0765% 1,235/1,614,232 alleles · rare exomes 1,135/1,461,884 · genomes 100/152,348 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.418%	239
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.0654%	1,529
Admixed American	0.025%	4,001
African / African-American	0.00933%	10,723
East Asian	0.00891%	11,222

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: SERPINE1
Protein: p.Ala119=
Coding: c.357G>A
MANE Select: NM_000602
dbSNP: rs6091
Type: single nucleotide variant
Location: chr7:101130506 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.03 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.68 · 29 PDB
Residue 119: a β-strand

Full SERPINE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital plasminogen activator inhibitor type 1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital plasminogen activator inhibitor type 1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

SERPINE1 p.Ala119Thr Uncertain significance ★ ⚠ same residue
SERPINE1 c.*617T>A Uncertain significance ★★ same condition
SERPINE1 p.Asp240Gly Uncertain significance ★★ ⚠ same condition
SERPINE1 p.Gly196Ser Uncertain significance ★★ ⚠ same condition
SERPINE1 p.Leu175Pro Uncertain significance ★★ ⚠ same condition
SERPINE1 c.1088-9C>T Benign/Likely benign ★★ same condition
SERPINE1 c.*1186C>T Benign ★★ same condition
SERPINE1 c.*1449C>T Benign ★★ 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/serpine1-p-ala119 (accessed [today's date]).

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