ABCD1 p.Glu302Met
c.904_905delinsAT · rs2091726242 · VCV872971
ClinGen expert panel — Peroxisomal Disorders VCEP
Uncertain Significance for adrenoleukodystrophy. Applied ACMG criteria (verbatim):
PM2_Supporting PP4
Curation rationale (ClinGen, verbatim)
The c.904_905delinsAT variant in ABCD1 is predicted to cause an in-frame substitution of glutamic acid by methionine at amino acid 302 (p.Glu302Met). At least one patient with this variant displayed rapid progression of inflammatory white matter demyelination in childhood and abnormal very long chain fatty acid testing , which is highly specific for adrenoleukodystrophy (PP4, PMID:33547378). This variant is absent from gnomAD v3.1.2, v2.1.1 and v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance due to insufficient evidence for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: PP4, PM2_Supporting (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic |
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ABCD1
- Protein
- p.Glu302Met
- Coding
- c.904_905delinsAT
- MANE Select
- NM_000033
- dbSNP
- rs2091726242
- Type
- Indel
- Location
- chrX:153729235 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
- Residue 302
- an α-helix; the abc transmembrane type-1 domain; a UniProt-annotated variant site (in ald)
Disease context
adrenoleukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor X-linked adrenoleukodystrophy (Orphanet):
- Inheritance
- X-linked dominant
- Onset
- Adolescent, Adult, Childhood, Elderly
- Prevalence
- 1-9 / 1 000 000 (Israel)
Similar variants
- ABCD1 p.Glu302Asp Likely pathogenic ★ same residue
- ABCD1 p.Glu302Lys Pathogenic ★ same residue
- ABCD1 p.Glu302Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- ABCD1 p.Glu302= Likely benign ★ same residue
- ABCD1 p.Ala206fs Likely pathogenic ★ same condition
- ABCD1 p.Arg6fs Pathogenic ★ same condition
- ABCD1 p.Glu292Ile Likely pathogenic ★ same condition
- ABCD1 p.Met1_Pro2delinsIleSer 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/abcd1-p-glu302met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown