Is SLC2A1 p.Trp186Ter (c.558G>A) pathogenic?

SLC2A1 p.Trp186Ter (c.558G>A) is classified Pathogenic in SLC2A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SLC2A1 p.Trp186Ter (c.558G>A)?

SLC2A1 p.Trp186Ter (c.558G>A) is associated with Inborn genetic diseases, encephalopathy due to GLUT1 deficiency (ClinVar).

How common is SLC2A1 p.Trp186Ter (c.558G>A) in the general population?

SLC2A1 p.Trp186Ter (c.558G>A) is absent from gnomAD v4.1 (gnomAD).

SLC2A1 p.Trp186Ter

c.558G>A · rs2124449417 · VCV1069398

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Trp186Ter
Coding: c.558G>A
MANE Select: NM_006516
dbSNP: rs2124449417
Type: single nucleotide variant
Location: chr1:42929994 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.30 · 5 PDB
Residue 186: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: encephalopathy due to GLUT1 deficiency

Similar variants

SLC2A1 p.Trp186Arg 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
SLC2A1 c.276-1G>A Pathogenic ★★ same condition
SLC2A1 c.680-11G>A 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-trp186ter (accessed [today's date]).

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