Is ABCD1 p.Pro42fs (c.125del) pathogenic?

ABCD1 p.Pro42fs (c.125del) is classified Likely pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Absent from gnomAD v4.1; Associated with X-linked cerebral adrenoleukodystrophy.

What condition is associated with ABCD1 p.Pro42fs (c.125del)?

ABCD1 p.Pro42fs (c.125del) is associated with X-linked cerebral adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Pro42fs (c.125del) in the general population?

ABCD1 p.Pro42fs (c.125del) is absent from gnomAD v4.1 (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Pro42fs

c.125del · rs2148388674 · VCV1679830

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,146,589)

Conditions

X-linked cerebral adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -0.73, phastCons 0.92

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,146,589). 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.Pro42fs
Coding: c.125del
MANE Select: NM_000033
dbSNP: rs2148388674
Type: Deletion
Location: chrX:153725388 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB

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

Disease context

X-linked cerebral 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 p.Pro42Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCD1 p.Ser606Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCD1 c.1394-2_1404del Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.901-48_909del Pathogenic/Likely pathogenic ★★ same type
ABCD1 p.Ala241fs Pathogenic ★★ same type
ABCD1 p.Arg80_Leu82del Pathogenic/Likely pathogenic ★★ same type
ABCD1 p.Gln472fs Pathogenic ★★ same type
ABCD1 p.Gln645fs Pathogenic/Likely pathogenic ★★ same type

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-pro42fs (accessed [today's date]).

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