Is SI p.Pro183fs (c.545dup) pathogenic?

SI p.Pro183fs (c.545dup) is classified Likely pathogenic in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Pro183fs (c.545dup)?

SI p.Pro183fs (c.545dup) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How is Congenital sucrase-isomaltase deficiency inherited?

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

SI p.Pro183fs

c.545dup · VCV3588895

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.54	GERP -3.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: SI
Protein: p.Pro183fs
Coding: c.545dup
MANE Select: NM_001041
Type: Duplication
Location: chr3:165067429 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.86 · 2 PDB
Residue 183: the 'isomaltase' region; an α-helix

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

Disease context

congenital sucrase-isomaltase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital sucrase-isomaltase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SI p.Gln677fs Pathogenic/Likely pathogenic ★★ same condition
SI p.His1210fs Pathogenic/Likely pathogenic ★★ same condition
SI p.Phe1366fs Pathogenic/Likely pathogenic ★★ same condition
SI c.119-11dup Benign/Likely benign ★★ same condition
SI c.2737-23dup Benign/Likely benign ★★ same condition
SI c.374-11dup Benign/Likely benign ★★ same condition
SI c.5198-20dup Benign/Likely benign ★★ same condition
SI p.Asn1535fs 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/si-p-pro183fs (accessed [today's date]).

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