Is SERPINE1 p.Val17Ile (c.49G>A) pathogenic?

SERPINE1 p.Val17Ile (c.49G>A) is classified Benign/Likely benign in SERPINE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.0889); Common (popmax 6.39%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital plasminogen activator inhibitor type 1 deficiency.

What condition is associated with SERPINE1 p.Val17Ile (c.49G>A)?

SERPINE1 p.Val17Ile (c.49G>A) is associated with congenital plasminogen activator inhibitor type 1 deficiency (ClinVar).

What do computational predictors say about SERPINE1 p.Val17Ile (c.49G>A)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

SERPINE1 p.Val17Ile

Q: How common is SERPINE1 p.Val17Ile (c.49G>A) in the general population?

SERPINE1 p.Val17Ile (c.49G>A) is common (popmax 6.39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.49G>A · rs6090 · VCV358307

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.39%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital plasminogen activator inhibitor type 1 deficiency

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.1
Regional constraint	o/e 0.86	unconstrained · MANE · 9,045 bp · p 0.0014 · regional, not allelic
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.39% African / African-American · 4,793/75,020 alleles

Filtering AF 6.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.18%

Overall 1.71% 27,522/1,614,080 alleles · common exomes 22,541/1,461,832 · genomes 4,981/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.39%	16
Finnishnot grpmax-eligible	5.65%	18
Admixed American	4.51%	22
East Asian	3.67%	27
Middle Eastern	2.56%	39
Remaining individualsnot grpmax-eligible	2.14%	47
Ashkenazi Jewishnot grpmax-eligible	1.77%	56
South Asian	1.56%	64
European (non-Finnish)	0.958%	104
Amishnot grpmax-eligible	0.548%	182

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.Val17Ile
Coding: c.49G>A
MANE Select: NM_000602
dbSNP: rs6090
Type: single nucleotide variant
Location: chr7:101128442 (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 17: a UniProt-annotated variant site (in)

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-val17ile (accessed [today's date]).

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