Is SI p.Glu613Ter (c.1837G>T) pathogenic?

SI p.Glu613Ter (c.1837G>T) is classified Pathogenic/Likely pathogenic in SI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-05). Very rare (popmax 0.00458%, nfe); Associated with SI-related disorder.

What condition is associated with SI p.Glu613Ter (c.1837G>T)?

SI p.Glu613Ter (c.1837G>T) is associated with SI-related disorder, congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Glu613Ter (c.1837G>T) in the general population?

SI p.Glu613Ter (c.1837G>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

SI p.Glu613Ter

c.1837G>T · rs201055347 · VCV1382544

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Conditions

SI-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 48
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -1.7, phastCons 0.73
Overall
CADD	39.0	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 0.00458% European (non-Finnish) · 54/1,179,522 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00335% 54/1,613,146 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.Glu613Ter
Coding: c.1837G>T
MANE Select: NM_001041
dbSNP: rs201055347
Type: single nucleotide variant
Location: chr3:165046891 (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 613: the 'isomaltase' region; an α-helix

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

Disease context

SI-related disorder

Also linked: congenital sucrase-isomaltase deficiency

Similar variants

SI c.2426+1G>A Likely pathogenic ★★ same condition
SI c.2737-2A>G 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

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-glu613ter (accessed [today's date]).

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