Is SERPINE1 p.Arg185= (c.555G>C) pathogenic?

SERPINE1 p.Arg185= (c.555G>C) is classified Benign in SERPINE1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Low-frequency (popmax 4%, sas); Associated with congenital plasminogen activator inhibitor type 1 deficiency.

What condition is associated with SERPINE1 p.Arg185= (c.555G>C)?

SERPINE1 p.Arg185= (c.555G>C) is associated with congenital plasminogen activator inhibitor type 1 deficiency (ClinVar).

How common is SERPINE1 p.Arg185= (c.555G>C) in the general population?

SERPINE1 p.Arg185= (c.555G>C) is low-frequency (popmax 4%, sas) (gnomAD).

SERPINE1 p.Arg185=

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.555G>C · rs201293550 · VCV358311

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.4
Overall
CADD	4.605	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4% South Asian · 3,644/91,066 alleles

Filtering AF 3.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.85%

Overall 0.247% 3,992/1,613,992 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4%	25
Middle Eastern	0.396%	252
Remaining individualsnot grpmax-eligible	0.238%	420
Admixed American	0.0167%	5,997
European (non-Finnish)	0.0131%	7,663
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
East Asian	0.00669%	14,947
Finnishnot grpmax-eligible	0.00625%	16,005
African / African-American	0.00267%	37,492

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.Arg185=
Coding: c.555G>C
MANE Select: NM_000602
dbSNP: rs201293550
Type: single nucleotide variant
Location: chr7:101131924 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.03 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.68 · 29 PDB

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.Arg185Gln 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-arg185 (accessed [today's date]).

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