Is SI p.Val342fs (c.1023del) pathogenic?

SI p.Val342fs (c.1023del) is classified Pathogenic/Likely pathogenic in SI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-19). Very rare (popmax 0.00267%, afr); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Val342fs (c.1023del)?

SI p.Val342fs (c.1023del) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Val342fs (c.1023del) in the general population?

SI p.Val342fs (c.1023del) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

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

SI p.Val342fs

c.1023del · rs1713910885 · VCV2114756

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 0.00267%, afr)

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 10 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.14	GERP -2.1, phastCons 0.001
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,790 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,611,236 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.Val342fs
Coding: c.1023del
MANE Select: NM_001041
dbSNP: rs1713910885
Type: Deletion
Location: chr3:165060025 (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 342: 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.Asn1403fs Pathogenic/Likely pathogenic ★★ same condition
SI p.Gln278fs Pathogenic/Likely pathogenic ★★ same condition
SI p.Leu1062_Tyr1063insTer Pathogenic/Likely pathogenic ★★ same condition
SI c.2737-11del Benign/Likely benign ★★ same condition
SI c.2737-12_2737-11del Benign/Likely benign ★★ same condition
SI c.2737-17_2737-11del Likely benign ★★ same condition
SI c.3634-5del Benign/Likely benign ★★ same condition
SI c.374-11del Benign/Likely benign ★★ 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-val342fs (accessed [today's date]).

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