Is SERPING1 p.Pro126fs (c.377del) pathogenic?

SERPING1 p.Pro126fs (c.377del) is classified Pathogenic in SERPING1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-30). No gnomAD frequency available for this variant; Associated with hereditary angioedema with C1Inh deficiency.

What condition is associated with SERPING1 p.Pro126fs (c.377del)?

SERPING1 p.Pro126fs (c.377del) is associated with hereditary angioedema with C1Inh deficiency (ClinVar).

How common is SERPING1 p.Pro126fs (c.377del) in the general population?

SERPING1 p.Pro126fs (c.377del) is no gnomAD frequency available for this variant (gnomAD).

How is Hereditary angioedema with C1Inh deficiency inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SERPING1 p.Pro126fs

c.377del · rs2495426294 · VCV1690315

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary angioedema with C1Inh deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP -4.6, phastCons 0.098

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SERPING1
Protein: p.Pro126fs
Coding: c.377del
MANE Select: NM_000062
dbSNP: rs2495426294
Type: Deletion
Location: chr11:57600203 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 126: a UniProt-annotated variant site (in hae1; phenotype consistent with hereditary angioedema type 2); an α-helix

Full SERPING1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary angioedema with C1Inh deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary angioedema with C1Inh deficiency (Orphanet):

Inheritance: Not applicable
Onset: Adult, Elderly

Similar variants

SERPING1 p.Leu395_Leu396insTer Pathogenic ★ same condition
SERPING1 p.Asn25fs Pathogenic same condition
SERPING1 p.His351fs Pathogenic same condition
SERPING1 p.Lys77_Ile78insTer Pathogenic same condition
SERPING1 p.Phe225del Pathogenic same condition
SERPING1 p.Pro58fs Pathogenic same condition
SERPING1 p.Thr339_Leu340insTer Pathogenic same condition
SERPING1 p.Val250fs Pathogenic 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/serping1-p-pro126fs (accessed [today's date]).

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