Is SERPING1 p.Thr96Pro (c.286A>C) pathogenic?

SERPING1 p.Thr96Pro (c.286A>C) is classified Uncertain significance in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0662); Ultra-rare (popmax 0.0421%, afr); Associated with Inborn genetic diseases.

What condition is associated with SERPING1 p.Thr96Pro (c.286A>C)?

SERPING1 p.Thr96Pro (c.286A>C) is associated with Inborn genetic diseases (ClinVar).

How common is SERPING1 p.Thr96Pro (c.286A>C) in the general population?

SERPING1 p.Thr96Pro (c.286A>C) is ultra-rare (popmax 0.0421%, afr) (gnomAD).

What do computational predictors say about SERPING1 p.Thr96Pro (c.286A>C)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

SERPING1 p.Thr96Pro

c.286A>C · VCV3440081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0421%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -10.85	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	0.209	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

Grpmax group 0.0421% African / African-American · 25/59,446 alleles

Filtering AF 0.0292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.0113% 137/1,209,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0421%	2,378
Middle Eastern	0.0417%	2,400
Admixed American	0.025%	3,999
East Asian	0.0241%	4,142
Finnishnot grpmax-eligible	0.0176%	5,666
Remaining individualsnot grpmax-eligible	0.0157%	6,354
Ashkenazi Jewishnot grpmax-eligible	0.0134%	7,465
European (non-Finnish)	0.00785%	12,745
South Asian	0.00476%	21,027

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.Thr96Pro
Coding: c.286A>C
MANE Select: NM_000062
Type: single nucleotide variant
Location: chr11:57600113 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 96: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SERPING1 c.51+3A>G Pathogenic ★★ same condition
SERPING1 p.Asp408Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
SERPING1 p.Pro498Leu Likely pathogenic ★★ ⚠ same condition
SERPING1 p.Asp144Gly Uncertain significance ★★ ⚠ same condition
SERPING1 p.Asp424Glu Uncertain significance ★★ ⚠ same condition
SERPING1 p.Gln180His Uncertain significance ★★ ⚠ same condition
SERPING1 p.His334Tyr Uncertain significance ★★ ⚠ same condition
SERPING1 p.Ile232Lys Uncertain significance ★★ ⚠ 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-thr96pro (accessed [today's date]).

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