Is SERPING1 p.Arg309Ter (c.925A>T) pathogenic?

SERPING1 p.Arg309Ter (c.925A>T) is classified Pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-16). Absent from gnomAD v4.1; Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Arg309Ter (c.925A>T)?

SERPING1 p.Arg309Ter (c.925A>T) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Arg309Ter (c.925A>T) in the general population?

SERPING1 p.Arg309Ter (c.925A>T) is absent from gnomAD v4.1 (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.Arg309Ter

c.925A>T · VCV3338032

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary angioedema type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP 0.54
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SERPING1
Protein: p.Arg309Ter
Coding: c.925A>T
MANE Select: NM_000062
Type: single nucleotide variant
Location: chr11:57606443 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 309: a β-strand; a disulfide bond

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 c.1030-1G>T Pathogenic ★★ same condition
SERPING1 c.51+1G>T Pathogenic ★★ same condition
SERPING1 c.51+3A>C Pathogenic/Likely pathogenic ★★ same condition
SERPING1 c.52-1G>A Pathogenic ★★ same condition
SERPING1 c.550+1G>A Pathogenic ★★ same condition
SERPING1 c.551-1G>C Pathogenic/Likely pathogenic ★★ same condition
SERPING1 c.551-2A>G Pathogenic ★★ same condition
SERPING1 c.686-2A>G 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-arg309ter (accessed [today's date]).

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