Is SLC2A2 p.Ser397Arg (c.1191T>G) pathogenic?

SLC2A2 p.Ser397Arg (c.1191T>G) is classified Uncertain significance in SLC2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). AlphaMissense: likely pathogenic (0.7046); Absent from gnomAD v4.1; Associated with glycogen storage disease due to GLUT2 deficiency.

What condition is associated with SLC2A2 p.Ser397Arg (c.1191T>G)?

SLC2A2 p.Ser397Arg (c.1191T>G) is associated with glycogen storage disease due to GLUT2 deficiency (ClinVar).

How common is SLC2A2 p.Ser397Arg (c.1191T>G) in the general population?

SLC2A2 p.Ser397Arg (c.1191T>G) is absent from gnomAD v4.1 (gnomAD).

How is Fanconi-Bickel syndrome inherited?

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

What do computational predictors say about SLC2A2 p.Ser397Arg (c.1191T>G)?

AlphaMissense predicts likely pathogenic (score 0.7046) — an in-silico prediction, not a clinical call.

SLC2A2 p.Ser397Arg

c.1191T>G · rs2108233305 · VCV1475879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7046 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease due to GLUT2 deficiency

Computational evidence

Protein change
AlphaMissense	0.7046	likely pathogenic
REVEL	0.612	indeterminate
SaProt	LLR -10.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.7, phastCons 0.99
Regional constraint	o/e 0.65	unconstrained · MANE · 7,108 bp · p 3.3e-06 · regional, not allelic
Overall
CADD	19.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC2A2
Protein: p.Ser397Arg
Coding: c.1191T>G
MANE Select: NM_000340
dbSNP: rs2108233305
Type: single nucleotide variant
Location: chr3:170998376 (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-ser397arg (accessed [today's date]).

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