Is SERPINE1 p.Asn232Ser (c.695A>G) pathogenic?

SERPINE1 p.Asn232Ser (c.695A>G) is classified Likely benign in SERPINE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.0928); Rare (popmax 0.216%, afr); Associated with SERPINE1-related disorder.

What condition is associated with SERPINE1 p.Asn232Ser (c.695A>G)?

SERPINE1 p.Asn232Ser (c.695A>G) is associated with SERPINE1-related disorder (ClinVar).

How common is SERPINE1 p.Asn232Ser (c.695A>G) in the general population?

SERPINE1 p.Asn232Ser (c.695A>G) is rare (popmax 0.216%, afr) (gnomAD).

What do computational predictors say about SERPINE1 p.Asn232Ser (c.695A>G)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

SERPINE1 p.Asn232Ser

c.695A>G · rs147003064 · VCV3039903

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.216%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

SERPINE1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.529	indeterminate
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 0.57, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 9,045 bp · p 0.0014 · regional, not allelic
Overall
CADD	22.4	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 0.216% African / African-American · 162/74,928 alleles

Filtering AF 0.189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.013% 210/1,613,690 alleles · rare exomes 107/1,461,686 · genomes 103/152,004 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.216%	463
Remaining individualsnot grpmax-eligible	0.024%	4,165
Admixed American	0.0217%	4,612
South Asian	0.0187%	5,356
European (non-Finnish)	0.000254%	393,289

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.Asn232Ser
Coding: c.695A>G
MANE Select: NM_000602
dbSNP: rs147003064
Type: single nucleotide variant
Location: chr7:101132064 (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 232: a β-strand

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

Disease context

SERPINE1-related disorder

Similar variants

SERPINE1 p.Phe38= Likely benign same condition
SERPINE1 c.*617T>A Uncertain significance ★★ same type
SERPINE1 p.Asp240Gly Uncertain significance ★★ ⚠ same type
SERPINE1 p.Gly196Ser Uncertain significance ★★ ⚠ same type
SERPINE1 p.Leu175Pro Uncertain significance ★★ ⚠ same type
SERPINE1 p.Phe157Leu Uncertain significance ★★ ⚠ same type
SERPINE1 p.Pro372Ala Uncertain significance ★★ ⚠ same type
SERPINE1 c.1088-106A>G Benign ★★ same type

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-asn232ser (accessed [today's date]).

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