Is SERPINE1 p.Val152= (c.456G>C) pathogenic?

SERPINE1 p.Val152= (c.456G>C) is classified Conflicting classifications of pathogenicity in SERPINE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-05-04). Ultra-rare (popmax 0.0672%, nfe); Associated with congenital plasminogen activator inhibitor type 1 deficiency.

What condition is associated with SERPINE1 p.Val152= (c.456G>C)?

SERPINE1 p.Val152= (c.456G>C) is associated with congenital plasminogen activator inhibitor type 1 deficiency (ClinVar).

How common is SERPINE1 p.Val152= (c.456G>C) in the general population?

SERPINE1 p.Val152= (c.456G>C) is ultra-rare (popmax 0.0672%, nfe) (gnomAD).

SERPINE1 p.Val152=

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.456G>C · rs200318916 · VCV358309

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0672%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -3.2, phastCons 0.13
Overall
CADD	4.849	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0672% European (non-Finnish) · 793/1,180,044 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0618%

Overall 0.0509% 822/1,614,094 alleles · ultra-rare exomes 785/1,461,880 · genomes 37/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0672%	1,488
Remaining individualsnot grpmax-eligible	0.032%	3,124
African / African-American	0.00934%	10,705
Admixed American	0.00333%	30,001

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.Val152=
Coding: c.456G>C
MANE Select: NM_000602
dbSNP: rs200318916
Type: single nucleotide variant
Location: chr7:101130605 (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 152: an α-helix

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 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
SERPINE1 c.*1737G>A 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-val152 (accessed [today's date]).

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