Is SLC2A2 p.Arg158Ser (c.474A>C) pathogenic?

SLC2A2 p.Arg158Ser (c.474A>C) is classified Likely pathogenic in SLC2A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-20). AlphaMissense: likely pathogenic (0.981); Absent from gnomAD v4.1; Associated with glycogen storage disease due to GLUT2 deficiency.

What condition is associated with SLC2A2 p.Arg158Ser (c.474A>C)?

SLC2A2 p.Arg158Ser (c.474A>C) is associated with glycogen storage disease due to GLUT2 deficiency, type 2 diabetes mellitus (ClinVar).

How common is SLC2A2 p.Arg158Ser (c.474A>C) in the general population?

SLC2A2 p.Arg158Ser (c.474A>C) 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.Arg158Ser (c.474A>C)?

AlphaMissense predicts likely pathogenic (score 0.981) — an in-silico prediction, not a clinical call.

SLC2A2 p.Arg158Ser

c.474A>C · rs2473906384 · VCV3064444

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to GLUT2 deficiency

Computational evidence

Protein change
AlphaMissense	0.981	likely pathogenic ✓ concordant with ClinVar · top 1% in SLC2A2
REVEL	0.879	moderately pathogenic-leaning
SaProt	LLR -14.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.16 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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.Arg158Ser
Coding: c.474A>C
MANE Select: NM_000340
dbSNP: rs2473906384
Type: single nucleotide variant
Location: chr3:171009980 (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

Also linked: type 2 diabetes mellitus

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.Arg228Ter Pathogenic ★★ same condition
SLC2A2 p.Arg301Ter Pathogenic ★★ same condition
SLC2A2 p.Arg365Ter Pathogenic ★★ same condition
SLC2A2 p.Glu84Ter Pathogenic/Likely pathogenic ★★ same condition
SLC2A2 p.Pro417Leu 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-arg158ser (accessed [today's date]).

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