Is SLC2A1 p.Pro479= (c.1437C>T) pathogenic?

SLC2A1 p.Pro479= (c.1437C>T) is classified Benign/Likely benign in SLC2A1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.095%, amr); Associated with hereditary cryohydrocytosis with reduced stomatin.

What condition is associated with SLC2A1 p.Pro479= (c.1437C>T)?

SLC2A1 p.Pro479= (c.1437C>T) is associated with hereditary cryohydrocytosis with reduced stomatin, dystonia 9, encephalopathy due to GLUT1 deficiency (ClinVar).

How common is SLC2A1 p.Pro479= (c.1437C>T) in the general population?

SLC2A1 p.Pro479= (c.1437C>T) is ultra-rare (popmax 0.095%, amr) (gnomAD).

SLC2A1 p.Pro479=

Q: How is Hereditary cryohydrocytosis with reduced stomatin inherited?

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

c.1437C>T · rs146879902 · VCV139168

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.095%, amr)

Conditions

hereditary cryohydrocytosis with reduced stomatin

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 -12	GERP -3.4
Overall
CADD	0.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.095% Admixed American · 57/60,024 alleles

Filtering AF 0.0835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0817%

Overall 0.0743% 1,199/1,614,140 alleles · ultra-rare exomes 1,104/1,461,886 · genomes 95/152,254 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
Admixed Americangrpmax	0.095%	1,053
European (non-Finnish)	0.088%	1,137
Remaining individualsnot grpmax-eligible	0.0576%	1,736
African / African-American	0.0213%	4,689
Finnishnot grpmax-eligible	0.00625%	16,008

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SLC2A1
Protein: p.Pro479=
Coding: c.1437C>T
MANE Select: NM_006516
dbSNP: rs146879902
Type: single nucleotide variant
Location: chr1:42927083 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.30 · 5 PDB
Residue 479: the 'disordered' region

Full SLC2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary cryohydrocytosis with reduced stomatin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dystonia 9 encephalopathy due to GLUT1 deficiency childhood onset GLUT1 deficiency syndrome 2 epilepsy, idiopathic generalized, susceptibility to, 12

For Hereditary cryohydrocytosis with reduced stomatin (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

SLC2A1 p.Pro479Thr Likely benign ★★ same residue
SLC2A1 p.Pro479His Uncertain significance ★ ⚠ same residue
SLC2A1 p.Pro479Leu Uncertain significance ★★ ⚠ same residue
SLC2A1 c.115-2A>C Pathogenic ★★ same condition
SLC2A1 c.115-2A>G Pathogenic ★★ same condition
SLC2A1 c.18+1G>A Pathogenic ★★ same condition
SLC2A1 c.19-2A>G Pathogenic ★★ same condition
SLC2A1 c.275+1G>C 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/slc2a1-p-pro479 (accessed [today's date]).

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