Is SERPING1 p.Thr95= (c.285C>A) pathogenic?

SERPING1 p.Thr95= (c.285C>A) is classified Conflicting classifications of pathogenicity in SERPING1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-05-20). Very rare (popmax 0.00834%, amr); Associated with hereditary angioedema type 1.

What condition is associated with SERPING1 p.Thr95= (c.285C>A)?

SERPING1 p.Thr95= (c.285C>A) is associated with hereditary angioedema type 1 (ClinVar).

How common is SERPING1 p.Thr95= (c.285C>A) in the general population?

SERPING1 p.Thr95= (c.285C>A) is very rare (popmax 0.00834%, amr) (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.Thr95=

c.285C>A · rs886048400 · VCV305022

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 0.00834%, amr)

Conditions

hereditary angioedema type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.3	GERP -3.1
Overall
CADD	0.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,944 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,613,342 alleles · very rare exomes 3/1,461,392 · genomes 2/151,950 · joint denominator

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.Thr95=
Coding: c.285C>A
MANE Select: NM_000062
dbSNP: rs886048400
Type: single nucleotide variant
Location: chr11:57600112 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 95: 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.Thr95Ile Likely benign ★★ ⚠ same residue
SERPING1 p.Thr95Pro Likely benign ★ 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

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-thr95 (accessed [today's date]).

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