Is SLC2A1 p.Pro399Arg (c.1196C>G) pathogenic?

SLC2A1 p.Pro399Arg (c.1196C>G) is classified Conflicting classifications of pathogenicity in SLC2A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-10). AlphaMissense: likely pathogenic (0.9225); Absent from gnomAD v4.1; Associated with GLUT1 deficiency syndrome 1, autosomal recessive.

What condition is associated with SLC2A1 p.Pro399Arg (c.1196C>G)?

SLC2A1 p.Pro399Arg (c.1196C>G) is associated with GLUT1 deficiency syndrome 1, autosomal recessive (ClinVar).

How common is SLC2A1 p.Pro399Arg (c.1196C>G) in the general population?

SLC2A1 p.Pro399Arg (c.1196C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC2A1 p.Pro399Arg (c.1196C>G)?

AlphaMissense predicts likely pathogenic (score 0.9225) — an in-silico prediction, not a clinical call.

SLC2A1 p.Pro399Arg

c.1196C>G · rs1643442142 · VCV1011273

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9225 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GLUT1 deficiency syndrome 1, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.9225	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -17.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 621 bp · p 3e-12 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC2A1
Protein: p.Pro399Arg
Coding: c.1196C>G
MANE Select: NM_006516
dbSNP: rs1643442142
Type: single nucleotide variant
Location: chr1:42927687 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.30 · 5 PDB
Residue 399: a turn

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 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
SLC2A1 p.Met96Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
SLC2A1 p.Pro211Ser 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-pro399arg (accessed [today's date]).

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