Is SLC2A2 p.Phe479= (c.1437C>T) pathogenic?

SLC2A2 p.Phe479= (c.1437C>T) is classified Conflicting classifications of pathogenicity in SLC2A2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 59.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease due to GLUT2 deficiency.

What condition is associated with SLC2A2 p.Phe479= (c.1437C>T)?

SLC2A2 p.Phe479= (c.1437C>T) is associated with glycogen storage disease due to GLUT2 deficiency, type 2 diabetes mellitus (ClinVar).

How is Fanconi-Bickel syndrome inherited?

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

SLC2A2 p.Phe479=

Q: How common is SLC2A2 p.Phe479= (c.1437C>T) in the general population?

SLC2A2 p.Phe479= (c.1437C>T) is common (popmax 59.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1437C>T · rs5398 · VCV130348

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 59.9%, afr) — too common for a highly-penetrant pathogenic allele

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 0.07	GERP -3.7, phastCons 0.015
Overall
CADD	1.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59.9% African / African-American · 44,884/74,910 alleles

Filtering AF 59.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.3%

Overall 30.3% 488,077/1,613,122 alleles · common exomes 431,072/1,461,168 · genomes 57,005/151,954 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	59.9%	2
Middle Eastern	32.8%	3
Remaining individualsnot grpmax-eligible	31.9%	3
Ashkenazi Jewishnot grpmax-eligible	31.8%	3
Admixed American	30.3%	3
European (non-Finnish)	28.9%	3
South Asian	27.8%	4
Finnishnot grpmax-eligible	26%	4
Amishnot grpmax-eligible	24.3%	4
East Asian	22.4%	4

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.Phe479=
Coding: c.1437C>T
MANE Select: NM_000340
dbSNP: rs5398
Type: single nucleotide variant
Location: chr3:170998041 (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.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-phe479 (accessed [today's date]).

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