Is SLC2A2 p.Ile196= (c.588C>T) pathogenic?

SLC2A2 p.Ile196= (c.588C>T) is classified Likely benign in SLC2A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0352%, sas); Associated with glycogen storage disease due to GLUT2 deficiency.

What condition is associated with SLC2A2 p.Ile196= (c.588C>T)?

SLC2A2 p.Ile196= (c.588C>T) is associated with glycogen storage disease due to GLUT2 deficiency (ClinVar).

How common is SLC2A2 p.Ile196= (c.588C>T) in the general population?

SLC2A2 p.Ile196= (c.588C>T) is ultra-rare (popmax 0.0352%, sas) (gnomAD).

How is Fanconi-Bickel syndrome inherited?

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

SLC2A2 p.Ile196=

c.588C>T · rs374624284 · VCV507994

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0352%, sas)

Conditions

glycogen storage disease due to GLUT2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.7, phastCons 1
Overall
CADD	7.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0352% South Asian · 32/91,016 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.0267% 430/1,611,540 alleles · ultra-rare exomes 400/1,459,444 · genomes 30/152,096 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0352%	2,844
European (non-Finnish)	0.0303%	3,300
Admixed American	0.0284%	3,520
Remaining individualsnot grpmax-eligible	0.0208%	4,798
Middle Eastern	0.0165%	6,054
African / African-American	0.012%	8,321
East Asian	0.00223%	44,808

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: SLC2A2
Protein: p.Ile196=
Coding: c.588C>T
MANE Select: NM_000340
dbSNP: rs374624284
Type: single nucleotide variant
Location: chr3:171007172 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.56

Full SLC2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to GLUT2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fanconi-Bickel syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SLC2A2 c.497-2A>G Pathogenic/Likely pathogenic ★★ same condition
SLC2A2 c.775+1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC2A2 c.963+1G>A Pathogenic ★★ same condition
SLC2A2 p.Arg158Ser Likely pathogenic ★★ same condition
SLC2A2 p.Arg228Ter Pathogenic ★★ same condition
SLC2A2 p.Arg301Ter Pathogenic ★★ same condition
SLC2A2 p.Arg365Ter Pathogenic ★★ same condition
SLC2A2 p.Glu84Ter Pathogenic/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/slc2a2-p-ile196 (accessed [today's date]).

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