Is SLC2A1 p.Ser4= (c.12C>T) pathogenic?

SLC2A1 p.Ser4= (c.12C>T) is classified Likely benign in SLC2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). Very rare (popmax 0.0096%, sas); Associated with GLUT1 deficiency syndrome 1, autosomal recessive.

What condition is associated with SLC2A1 p.Ser4= (c.12C>T)?

SLC2A1 p.Ser4= (c.12C>T) is associated with GLUT1 deficiency syndrome 1, autosomal recessive (ClinVar).

How common is SLC2A1 p.Ser4= (c.12C>T) in the general population?

SLC2A1 p.Ser4= (c.12C>T) is very rare (popmax 0.0096%, sas) (gnomAD).

SLC2A1 p.Ser4=

c.12C>T · rs1295646319 · VCV2162596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0096%, sas)

Conditions

GLUT1 deficiency syndrome 1, autosomal recessive

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 5.4	GERP 0.33, phastCons 1
Overall
CADD	16.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0096% South Asian · 8/83,338 alleles

Filtering AF 0.00472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00347%

Overall 0.000652% 10/1,532,702 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0096%	10,417
European (non-Finnish)	0.000175%	572,073

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.Ser4=
Coding: c.12C>T
MANE Select: NM_006516
dbSNP: rs1295646319
Type: single nucleotide variant
Location: chr1:42958640 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.30 · 5 PDB

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

Disease context

GLUT1 deficiency syndrome 1, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC2A1 p.Ser4Asn Uncertain significance ★★ ⚠ same residue
SLC2A1 p.Ser4Gly Uncertain significance ★ ⚠ same residue
SLC2A1 c.1279-2A>G Likely pathogenic ★★ same condition
SLC2A1 c.-107G>A Pathogenic/Likely pathogenic ★★ same condition
SLC2A1 p.Asn34Asp Pathogenic/Likely pathogenic ★★ same condition
SLC2A1 p.Gln200Ter Pathogenic/Likely pathogenic ★★ same condition
SLC2A1 p.Leu215Phe Likely pathogenic ★★ same condition
SLC2A1 p.Met420Thr 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-ser4 (accessed [today's date]).

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