Is SERPING1 p.Ser240Pro (c.718T>C) pathogenic?

SERPING1 p.Ser240Pro (c.718T>C) is classified Likely pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-07). AlphaMissense: likely pathogenic (0.9287); Absent from gnomAD v4.1; Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Ser240Pro (c.718T>C)?

SERPING1 p.Ser240Pro (c.718T>C) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Ser240Pro (c.718T>C) in the general population?

SERPING1 p.Ser240Pro (c.718T>C) 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.

What do computational predictors say about SERPING1 p.Ser240Pro (c.718T>C)?

AlphaMissense predicts likely pathogenic (score 0.9287) — an in-silico prediction, not a clinical call.

SERPING1 p.Ser240Pro

c.718T>C · rs2495440471 · VCV3252007

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9287 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary angioedema type 1

Computational evidence

Protein change
AlphaMissense	0.9287	likely pathogenic ✓ concordant with ClinVar · top 3% in SERPING1
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -14.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser240Pro
Coding: c.718T>C
MANE Select: NM_000062
dbSNP: rs2495440471
Type: single nucleotide variant
Location: chr11:57606042 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 240: an α-helix

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-ser240pro (accessed [today's date]).

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