Is SERPING1 p.Pro105fs (c.312dup) pathogenic?

SERPING1 p.Pro105fs (c.312dup) is classified Pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-15). No gnomAD frequency available for this variant; Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Pro105fs (c.312dup)?

SERPING1 p.Pro105fs (c.312dup) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Pro105fs (c.312dup) in the general population?

SERPING1 p.Pro105fs (c.312dup) 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.Pro105fs

c.312dup · rs2495426038 · VCV3242425

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.17	GERP -4.4

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.Pro105fs
Coding: c.312dup
MANE Select: NM_000062
dbSNP: rs2495426038
Type: Duplication
Location: chr11:57600137 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 105: the 'disordered' region; the '7 x 4 aa tandem repeats of [qe]-p-t-[tq]' region; a UniProt-annotated variant site (in hae1; phenotype consistent with hereditary angioedema type 2)

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-pro105fs (accessed [today's date]).

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