ABCD1 p.Val250=
c.750G>C · rs782196006 · VCV193032
ClinGen expert panel — Peroxisomal Disorders VCEP
Likely Benign for adrenoleukodystrophy. Applied ACMG criteria (verbatim):
PM2_Supporting BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.750G>C (NM_000033.4) variant in ABCD1 is a variant occurring in exon 1. This variant is absent from gnomAD v2.1.1 and v3.1.2. It is reported in gnomAD v4.1 at a frequency of 0.000001120 (1/892612 alleles) in the non-Finnish European population with no hemizygotes, which is below the threshold of 0.0000017 set by the Peroxisomal Disorders VCEP (PM2_Supporting). The results from SpliceAI in silico predictor give a score of 0, which suggests that the variant does not impact ABCD1 function (BP4, BP7). Although the Bayesian points system suggests that a total of -1 pt can yield a likely benign classification, it is conservative to assume a minimum score of -2 pts for likely benign classifications. In summary, the Peroxisomal Disorders VCEP classified the variant as likely benign using the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders Variant Curation Expert Panel: PM2_supporting, BP4, BP7 (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 · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 5.591 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
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
- ABCD1
- Protein
- p.Val250=
- Coding
- c.750G>C
- MANE Select
- NM_000033
- dbSNP
- rs782196006
- Type
- single nucleotide variant
- Location
- chrX:153726016 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
- Residue 250
- an α-helix; the abc transmembrane type-1 domain
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.Val250Met Uncertain significance ★★ ⚠ same residue
- ABCD1 p.Val250Leu Uncertain significance ★ ⚠ same residue
- ABCD1 c.1635-2A>G Pathogenic ★★ same condition
- ABCD1 c.1781-1G>C Pathogenic ★★ same condition
- ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
- ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCD1 c.1866-1G>C Likely pathogenic ★★ same condition
- ABCD1 c.1866-2A>T 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/abcd1-p-val250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown