Is SERPINI1 p.Pro293= (c.879C>T) pathogenic?

SERPINI1 p.Pro293= (c.879C>T) is classified Likely benign in SERPINI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Absent from gnomAD v4.1; Associated with familial encephalopathy with neuroserpin inclusion bodies.

What condition is associated with SERPINI1 p.Pro293= (c.879C>T)?

SERPINI1 p.Pro293= (c.879C>T) is associated with familial encephalopathy with neuroserpin inclusion bodies (ClinVar).

How common is SERPINI1 p.Pro293= (c.879C>T) in the general population?

SERPINI1 p.Pro293= (c.879C>T) is absent from gnomAD v4.1 (gnomAD).

SERPINI1 p.Pro293=

Q: How is Familial encephalopathy with neuroserpin inclusion bodies inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.879C>T · rs2476236146 · VCV2083343

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial encephalopathy with neuroserpin inclusion bodies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.38	GERP 1.7, phastCons 0.99
Overall
CADD	13.03	PHRED · no single calibrated threshold — expert panels disagree

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: SERPINI1
Protein: p.Pro293=
Coding: c.879C>T
MANE Select: NM_001122752
dbSNP: rs2476236146
Type: single nucleotide variant
Location: chr3:167794822 (GRCh38)
Gene constraint: LOEUF 0.459 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 88.79 · 3 PDB
Residue 293: a β-strand

Full SERPINI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial encephalopathy with neuroserpin inclusion bodies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial encephalopathy with neuroserpin inclusion bodies (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

SERPINI1 p.Gly392Glu Pathogenic/Likely pathogenic ★★ same condition
SERPINI1 p.Ala19Thr Uncertain significance ★★ ⚠ same condition
SERPINI1 p.Ala280Ser Uncertain significance ★★ ⚠ same condition
SERPINI1 p.Asn281His Uncertain significance ★★ ⚠ same condition
SERPINI1 p.Asn345Asp Uncertain significance ★★ ⚠ same condition
SERPINI1 p.Asp305Val Uncertain significance ★★ ⚠ same condition
SERPINI1 p.Asp327Val Uncertain significance ★★ ⚠ same condition
SERPINI1 p.Glu101Val 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/serpini1-p-pro293 (accessed [today's date]).

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