Is SERPING1 p.His334Pro (c.1001A>C) pathogenic?

SERPING1 p.His334Pro (c.1001A>C) is classified Likely pathogenic in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: ambiguous (0.4723); Absent from gnomAD v4.1; Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.His334Pro (c.1001A>C)?

SERPING1 p.His334Pro (c.1001A>C) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.His334Pro (c.1001A>C) in the general population?

SERPING1 p.His334Pro (c.1001A>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.His334Pro (c.1001A>C)?

AlphaMissense predicts ambiguous (score 0.4723) — an in-silico prediction, not a clinical call.

SERPING1 p.His334Pro

c.1001A>C · rs766491693 · VCV3242454

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4723 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary angioedema type 1

Computational evidence

Protein change
AlphaMissense	0.4723	ambiguous
REVEL	0.659	pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.071, phastCons 0.98
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	22.6	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.His334Pro
Coding: c.1001A>C
MANE Select: NM_000062
dbSNP: rs766491693
Type: single nucleotide variant
Location: chr11:57606519 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 334: 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.His334Tyr Uncertain significance ★★ ⚠ 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-his334pro (accessed [today's date]).

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