Is SLC2A2 p.Pro80= (c.240T>C) pathogenic?

SLC2A2 p.Pro80= (c.240T>C) is classified Likely benign in SLC2A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-27). Ultra-rare (popmax 0.0164%, mid); Associated with glycogen storage disease due to GLUT2 deficiency.

What condition is associated with SLC2A2 p.Pro80= (c.240T>C)?

SLC2A2 p.Pro80= (c.240T>C) is associated with glycogen storage disease due to GLUT2 deficiency (ClinVar).

How common is SLC2A2 p.Pro80= (c.240T>C) in the general population?

SLC2A2 p.Pro80= (c.240T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Fanconi-Bickel syndrome inherited?

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

SLC2A2 p.Pro80=

c.240T>C · rs756220231 · VCV385035

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -1.7	GERP -3.3
Overall
CADD	0.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,613,988 alleles · ultra-rare exomes 27/1,461,868 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00223%	44,892
European (non-Finnish)	0.00203%	49,167
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00134%	74,890

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.Pro80=
Coding: c.240T>C
MANE Select: NM_000340
dbSNP: rs756220231
Type: single nucleotide variant
Location: chr3:171014600 (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 p.Pro80fs Pathogenic ★ same residue
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

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-pro80 (accessed [today's date]).

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