Is SERPING1 p.Pro489fs (c.1466del) pathogenic?

SERPING1 p.Pro489fs (c.1466del) is classified Likely pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Associated with SERPING1-related disorder.

What condition is associated with SERPING1 p.Pro489fs (c.1466del)?

SERPING1 p.Pro489fs (c.1466del) is associated with SERPING1-related disorder (ClinVar).

SERPING1 p.Pro489fs

c.1466del · VCV4911673

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

SERPING1-related disorder

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 in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP -0.23, phastCons 1

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

Variant & gene context

Gene: SERPING1
Protein: p.Pro489fs
Coding: c.1466del
MANE Select: NM_000062
Type: Deletion
Location: chr11:57614542 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 489: a β-strand; 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

SERPING1-related disorder

Similar variants

SERPING1 p.Ala373fs Likely pathogenic ★ same condition
SERPING1 p.Asn272fs Pathogenic ★ same condition
SERPING1 p.Leu353fs Likely pathogenic ★ same condition
SERPING1 p.Pro489Arg Pathogenic ★ same residue
SERPING1 p.Ser176fs Likely pathogenic ★ same condition
SERPING1 p.Pro489Ala Uncertain significance ★ same residue
SERPING1 c.-99delC Likely benign same condition
SERPING1 c.551-2A>G 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-pro489fs (accessed [today's date]).

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