Is SERPING1 p.Pro110= (c.330A>G) pathogenic?

SERPING1 p.Pro110= (c.330A>G) is classified Conflicting classifications of pathogenicity in SERPING1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-05-05). Very rare (popmax 0.00146%, nfe); Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Pro110= (c.330A>G)?

SERPING1 p.Pro110= (c.330A>G) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Pro110= (c.330A>G) in the general population?

SERPING1 p.Pro110= (c.330A>G) is very rare (popmax 0.00146%, nfe) (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.Pro110=

c.330A>G · rs1371887844 · VCV879581

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00146%, nfe)

Conditions

hereditary angioedema type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.5
Overall
CADD	2.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00146% European (non-Finnish) · 16/1,096,726 alleles

Filtering AF 0.000864% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000699%

Overall 0.00116% 17/1,465,890 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00146%	68,545
South Asian	0.00113%	88,848

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SERPING1
Protein: p.Pro110=
Coding: c.330A>G
MANE Select: NM_000062
dbSNP: rs1371887844
Type: single nucleotide variant
Location: chr11:57600157 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 110: 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.Pro110fs Pathogenic ★ same residue
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

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-pro110 (accessed [today's date]).

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