Is SERPINE1 p.Pro312Ser (c.934C>T) pathogenic?

SERPINE1 p.Pro312Ser (c.934C>T) is classified Uncertain significance in SERPINE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.2389); Absent from gnomAD v4.1; Associated with congenital plasminogen activator inhibitor type 1 deficiency.

What condition is associated with SERPINE1 p.Pro312Ser (c.934C>T)?

SERPINE1 p.Pro312Ser (c.934C>T) is associated with congenital plasminogen activator inhibitor type 1 deficiency (ClinVar).

How common is SERPINE1 p.Pro312Ser (c.934C>T) in the general population?

SERPINE1 p.Pro312Ser (c.934C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SERPINE1 p.Pro312Ser (c.934C>T)?

AlphaMissense predicts likely benign (score 0.2389) — an in-silico prediction, not a clinical call.

SERPINE1 p.Pro312Ser

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.934C>T · rs1796546340 · VCV910008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2389 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital plasminogen activator inhibitor type 1 deficiency

Computational evidence

Protein change
AlphaMissense	0.2389	likely benign
REVEL	0.359	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.62, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 9,045 bp · p 0.0014 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: SERPINE1
Protein: p.Pro312Ser
Coding: c.934C>T
MANE Select: NM_000602
dbSNP: rs1796546340
Type: single nucleotide variant
Location: chr7:101135528 (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 312: 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-pro312ser (accessed [today's date]).

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