Is ABCD1 p.Ile657del (c.1970_1972del) pathogenic?

ABCD1 p.Ile657del (c.19701972del) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-03). Absent from gnomAD; Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Ile657del (c.1970_1972del)?

ABCD1 p.Ile657del (c.1970_1972del) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ile657del (c.1970_1972del) in the general population?

ABCD1 p.Ile657del (c.1970_1972del) is absent from gnomAD (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ABCD1 p.Ile657del

c.1970_1972del · rs2148399308 · VCV1256208

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

adrenoleukodystrophy

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 7.5	GERP 1.6, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Population frequency

dbSNP / gnomAD

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.Ile657del
Coding: c.1970_1972del
MANE Select: NM_000033
dbSNP: rs2148399308
Type: Deletion
Location: chrX:153743323 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 657: a UniProt-annotated variant site (in ald; cald-type); a β-strand; the abc transporter domain

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

adrenoleukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked adrenoleukodystrophy (Orphanet):

Inheritance: X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 1 000 000 (Israel)

Similar variants

ABCD1 c.1394-2_1404del Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.901-48_909del Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Ala241fs Pathogenic ★★ same condition
ABCD1 p.Arg80_Leu82del Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Gln472fs Pathogenic ★★ same condition
ABCD1 p.Gln645fs Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Glu371fs Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Glu477fs 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-ile657del (accessed [today's date]).

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