Is SLC2A1 p.Phe86= (c.258C>T) pathogenic?

SLC2A1 p.Phe86= (c.258C>T) is classified Conflicting classifications of pathogenicity in SLC2A1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-04-03). Ultra-rare (popmax 0.0253%, sas); Associated with hereditary cryohydrocytosis with reduced stomatin.

What condition is associated with SLC2A1 p.Phe86= (c.258C>T)?

SLC2A1 p.Phe86= (c.258C>T) is associated with hereditary cryohydrocytosis with reduced stomatin, dystonia 9, encephalopathy due to GLUT1 deficiency (ClinVar).

How common is SLC2A1 p.Phe86= (c.258C>T) in the general population?

SLC2A1 p.Phe86= (c.258C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

SLC2A1 p.Phe86=

Q: How is Hereditary cryohydrocytosis with reduced stomatin inherited?

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

c.258C>T · rs147319894 · VCV207180

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

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 0.14	GERP -3.7, phastCons 0.11
Overall
CADD	9.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,084 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.012% 193/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
European (non-Finnish)	0.0136%	7,375
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00534%	18,734
Admixed American	0.00333%	30,004

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.Phe86=
Coding: c.258C>T
MANE Select: NM_006516
dbSNP: rs147319894
Type: single nucleotide variant
Location: chr1:42931063 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.30 · 5 PDB
Residue 86: an α-helix

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 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
SLC2A1 c.276-1G>A Pathogenic ★★ same condition
SLC2A1 c.680-11G>A Pathogenic ★★ same condition
SLC2A1 p.Ala275Thr 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/slc2a1-p-phe86 (accessed [today's date]).

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