Is ABCD1 p.Trp664fs (c.1988dup) pathogenic?

ABCD1 p.Trp664fs (c.1988dup) is classified Pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-24). Absent from gnomAD; Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Trp664fs (c.1988dup)?

ABCD1 p.Trp664fs (c.1988dup) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Trp664fs (c.1988dup) in the general population?

ABCD1 p.Trp664fs (c.1988dup) 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.Trp664fs

c.1988dup · rs2148399327 · VCV1454919

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (9 of 10, 4 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -2.3, phastCons 0.97
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

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.Trp664fs
Coding: c.1988dup
MANE Select: NM_000033
dbSNP: rs2148399327
Type: Duplication
Location: chrX:153743342 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 664: the 'required for homodimerization' region; an α-helix; 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 p.Trp664Ter Pathogenic ★★ same residue
ABCD1 p.Arg80_Leu82dup Pathogenic ★★ same condition
ABCD1 p.Arg85fs Pathogenic ★★ same condition
ABCD1 p.Arg8fs Likely pathogenic ★★ same condition
ABCD1 p.Asn13fs Pathogenic ★★ same condition
ABCD1 p.Glu359fs Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Thr483fs Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Ala443fs 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-trp664fs (accessed [today's date]).

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