Is SERPING1 p.Pro248Arg (c.743C>G) pathogenic?

SERPING1 p.Pro248Arg (c.743C>G) is classified Conflicting classifications of pathogenicity in SERPING1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.8612); Absent from gnomAD v4.1; Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Pro248Arg (c.743C>G)?

SERPING1 p.Pro248Arg (c.743C>G) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Pro248Arg (c.743C>G) in the general population?

SERPING1 p.Pro248Arg (c.743C>G) 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.Pro248Arg (c.743C>G)?

AlphaMissense predicts likely pathogenic (score 0.8612) — an in-silico prediction, not a clinical call.

SERPING1 p.Pro248Arg

c.743C>G · rs2495440609 · VCV2735611

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8612 · 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	0.8612	likely pathogenic · top 6% in SERPING1
REVEL	0.743	pathogenic-leaning
SaProt	LLR -15.76	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 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	25.2	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.Pro248Arg
Coding: c.743C>G
MANE Select: NM_000062
dbSNP: rs2495440609
Type: single nucleotide variant
Location: chr11:57606067 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB

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-pro248arg (accessed [today's date]).

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