Is SI p.Ser982fs (c.2945_2946del) pathogenic?

SI p.Ser982fs (c.29452946del) is classified Pathogenic/Likely pathogenic in SI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-25). Very rare (popmax 0.00017%, nfe); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Ser982fs (c.2945_2946del)?

SI p.Ser982fs (c.2945_2946del) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Ser982fs (c.2945_2946del) in the general population?

SI p.Ser982fs (c.2945_2946del) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

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

SI p.Ser982fs

c.2945_2946del · rs751263307 · VCV2030530

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 26 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,880 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,459,206 alleles · very rare

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: SI
Protein: p.Ser982fs
Coding: c.2945_2946del
MANE Select: NM_001041
dbSNP: rs751263307
Type: Microsatellite
Location: chr3:165023723 (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 982: the 'isomaltase' region

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.Asp885fs Pathogenic/Likely pathogenic ★★ same condition
SI p.Gly92fs Pathogenic ★★ same condition
SI c.2302-4_2302-2del Likely pathogenic ★ same condition
SI p.Gly1113fs Likely pathogenic ★ same condition
SI c.1278+6_1278+8del Uncertain significance ★ same condition
SI p.Gln450del Uncertain significance ★ same condition
SI p.Met1196fs Conflicting classifications of pathogenicity ★ same condition
SI c.2426+1G>A 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-ser982fs (accessed [today's date]).

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