Is SERPING1 p.Arg249fs (c.744dup) pathogenic?

SERPING1 p.Arg249fs (c.744dup) is classified Pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Arg249fs (c.744dup)?

SERPING1 p.Arg249fs (c.744dup) 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.Arg249fs

c.744dup · VCV3336808

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	predicted	premature termination codon in exon 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 1.2, phastCons 0.85

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

Variant & gene context

Gene: SERPING1
Protein: p.Arg249fs
Coding: c.744dup
MANE Select: NM_000062
Type: Duplication
Location: chr11:57606064 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB

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.Glu451fs Pathogenic ★★ same condition
SERPING1 p.Lys201fs Pathogenic ★★ same condition
SERPING1 c.685+4dup Likely pathogenic ★ same condition
SERPING1 p.Ala209fs Pathogenic ★ same condition
SERPING1 p.Asn317fs Pathogenic ★ same condition
SERPING1 p.Gly453fs Likely pathogenic ★ same condition
SERPING1 p.Ile50fs Likely pathogenic ★ same condition
SERPING1 p.Leu37fs 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-arg249fs (accessed [today's date]).

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