Is SERPING1 p.Val378fs (c.1127_1130dup) pathogenic?

SERPING1 p.Val378fs (c.11271130dup) is classified Pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). No gnomAD frequency available for this variant; Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Val378fs (c.1127_1130dup)?

SERPING1 p.Val378fs (c.1127_1130dup) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Val378fs (c.1127_1130dup) in the general population?

SERPING1 p.Val378fs (c.1127_1130dup) 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.Val378fs

c.1127_1130dup · rs2495452487 · VCV3242573

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.35	GERP -2.4

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.Val378fs
Coding: c.1127_1130dup
MANE Select: NM_000062
dbSNP: rs2495452487
Type: Duplication
Location: chr11:57611812 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 378: an α-helix

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.Arg249fs Pathogenic ★ same condition
SERPING1 p.Asn317fs Pathogenic ★ same condition
SERPING1 p.Gly453fs Likely pathogenic ★ same condition
SERPING1 p.Ile50fs Likely 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-val378fs (accessed [today's date]).

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