Is SERPING1 p.Ser406fs (c.1216del) pathogenic?

SERPING1 p.Ser406fs (c.1216del) is classified Pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Ser406fs (c.1216del)?

SERPING1 p.Ser406fs (c.1216del) is associated with hereditary angioedema type 1 (ClinVar).

How is Hereditary angioedema with C1Inh deficiency inherited?

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

SERPING1 p.Ser406fs

c.1216del · VCV3255530

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary angioedema type 1

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (7 of 8, 33 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -0.2, phastCons 0.97

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

Variant & gene context

Gene: SERPING1
Protein: p.Ser406fs
Coding: c.1216del
MANE Select: NM_000062
Type: Deletion
Location: chr11:57611903 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 406: a β-strand

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

Disease context

hereditary angioedema type 1 — 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.Ser406= Benign ★★ same residue
SERPING1 p.Leu386fs Pathogenic/Likely pathogenic ★★ same condition
SERPING1 p.Phe55fs Pathogenic ★★ same condition
SERPING1 p.Ser283fs Pathogenic ★★ same condition
SERPING1 c.1029+1del Pathogenic ★ same condition
SERPING1 c.1030delG Pathogenic ★ same condition
SERPING1 c.685+1del Pathogenic ★ same condition
SERPING1 c.990_1029+16del 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-ser406fs (accessed [today's date]).

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