ABCD1 p.Thr18=
c.54G>A · rs781855598 · VCV444828
ClinGen expert panel — Peroxisomal Disorders VCEP
Likely Benign for adrenoleukodystrophy. Applied ACMG criteria (verbatim):
BS1 BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.54G>A variant (NM_000033.4) is a synonymous (silent) variant (p.Thr18=) that is not predicted by SpliceAI to impact splicing. The filtering allele frequency (the lower threshold of the 95% CI of 41/1036386) of the c.55G>T (p.Ala19Ser) variant in ABCD1 is 0.00002617 for non-Finnish European exomes by gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold (>=0.000017) for BS1, and therefore meets this criterion (BS1). 10 hemizygotes are noted in gnomAD v4.1 for this variant. The computational splicing predictor SpliceAI gives a score of 0 for donor and acceptor loss and gain, suggesting that the variant has no impact on splicing. The exonic variant in exon 1 is not located in the first or last three bases of the exon. (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for X-linked ABCD1 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: BS1, 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 0.081 | GERP -3.1, phastCons 0.18 |
| Overall | ||
| CADD | 1.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0286% | 3,500 |
| European (non-Finnish)grpmax | 0.0045% | 22,208 |
| Remaining individualsnot grpmax-eligible | 0.00221% | 45,163 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Thr18=
- Coding
- c.54G>A
- MANE Select
- NM_000033
- dbSNP
- rs781855598
- Type
- single nucleotide variant
- Location
- chrX:153725320 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
Similar variants
- ABCD1 p.Thr18Lys Likely benign ★ same residue
- ABCD1 p.Thr18Met 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-thr18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown