Is SI c.1887+8A>C pathogenic?

SI c.1887+8A>C is classified Likely benign in SI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-04). Very rare (popmax 0.00469%, nfe); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI c.1887+8A>C?

SI c.1887+8A>C is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI c.1887+8A>C in the general population?

SI c.1887+8A>C is very rare (popmax 0.00469%, nfe) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

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

SI c.1887+8A>C

rs372410648 · VCV1632678

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00469%, nfe)

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +8	near-intronic (+8 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -2.8
Non-coding constraint	Z -0.33	1 kb window · o/e 1.04 · regional · uncalibrated
Overall
CADD	0.899	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00469% European (non-Finnish) · 55/1,172,796 alleles

Filtering AF 0.00369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00331%

Overall 0.00349% 56/1,605,502 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00469%	21,324
Remaining individualsnot grpmax-eligible	0.00161%	62,186

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
Coding: c.1887+8A>C
MANE Select: NM_001041
dbSNP: rs372410648
Type: single nucleotide variant
Location: chr3:165046833 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.86 · 2 PDB

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 c.2426+1G>A Likely pathogenic ★★ same condition
SI c.2893-1G>A Likely pathogenic ★★ same condition
SI c.3099+1G>C Likely pathogenic ★★ same condition
SI c.3521-1G>T Likely pathogenic ★★ same condition
SI c.373+1G>A Likely pathogenic ★★ same condition
SI c.4575+2T>C Likely pathogenic ★★ same condition
SI c.4927-1G>A Likely pathogenic ★★ same condition
SI c.5248-2A>C 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-c-1887-plus-8a-c (accessed [today's date]).

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