Is SERPING1 p.Ser406= (c.1218C>T) pathogenic?

SERPING1 p.Ser406= (c.1218C>T) is classified Benign in SERPING1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Low-frequency (popmax 4.3%, afr); Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Ser406= (c.1218C>T)?

SERPING1 p.Ser406= (c.1218C>T) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Ser406= (c.1218C>T) in the general population?

SERPING1 p.Ser406= (c.1218C>T) is low-frequency (popmax 4.3%, afr) (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.Ser406=

c.1218C>T · rs11229070 · VCV305028

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.3%, afr)

Conditions

hereditary angioedema type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.14	GERP -2.5, phastCons 0.004
Overall
CADD	8.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.3% African / African-American · 3,229/75,012 alleles

Filtering AF 4.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.13%

Overall 0.228% 3,679/1,614,110 alleles · low-frequency exomes 1,763/1,461,816 · genomes 1,916/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.3%	23
Admixed American	0.315%	318
Remaining individualsnot grpmax-eligible	0.293%	342
Middle Eastern	0.15%	669
South Asian	0.00988%	10,120
European (non-Finnish)	0.005%	20,001
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Ser406=
Coding: c.1218C>T
MANE Select: NM_000062
dbSNP: rs11229070
Type: single nucleotide variant
Location: chr11:57611905 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 406: a β-strand

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.Ser406fs 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-ser406 (accessed [today's date]).

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