ABCD1 p.Ala205=
c.615G>A · rs782601474 · VCV774266
ClinGen expert panel — Peroxisomal Disorders VCEP
Benign for adrenoleukodystrophy. Applied ACMG criteria (verbatim):
BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
The NM_000033.4(ABCD1):c.615G>A (p.Ala205=) variant is a synonymous variant that is outside of the splice region and not predicted by SpliceAI to impact splicing (BP4, BP7). The GrpMax filtering allele frequency of the c.615G>A variant in ABCD1 is 0.002175, gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold of ≥0.00017 for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: BA1, 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 -5 | GERP -3.4 |
| Overall | ||
| CADD | 2.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.251% | 398 |
| Middle Eastern | 0.023% | 4,356 |
| Remaining individualsnot grpmax-eligible | 0.0126% | 7,936 |
| East Asian | 0.00592% | 16,896 |
| African / African-American | 0.0052% | 19,246 |
| European (non-Finnish) | 0.000782% | 127,923 |
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.Ala205=
- Coding
- c.615G>A
- MANE Select
- NM_000033
- dbSNP
- rs782601474
- Type
- single nucleotide variant
- Location
- chrX:153725881 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
- Residue 205
- 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.Ala205Glu Conflicting classifications of pathogenicity ★ ⚠ 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
- ABCD1 c.901-1G>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/abcd1-p-ala205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown