Is ABCD1 p.Arg85fs (c.253dup) pathogenic?

ABCD1 p.Arg85fs (c.253dup) is classified Pathogenic in ABCD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-24). Absent from gnomAD; Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Arg85fs (c.253dup)?

ABCD1 p.Arg85fs (c.253dup) is associated with ABCD1-related disorder, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg85fs (c.253dup) in the general population?

ABCD1 p.Arg85fs (c.253dup) is absent from gnomAD (gnomAD).

ABCD1 p.Arg85fs

c.253dup · rs713993050 · VCV162148

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ABCD1-related disorder

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 7.8	GERP 1.5, phastCons 1

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.Arg85fs
Coding: c.253dup
MANE Select: NM_000033
dbSNP: rs713993050
Type: Duplication
Location: chrX:153725514 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 85: a β-strand; the 'interaction with pex19' region

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

Disease context

ABCD1-related disorder

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Arg85_Leu93del Uncertain significance ★ same residue
ABCD1 p.Arg85Leu Uncertain significance ★ ⚠ same residue
ABCD1 p.Arg85Pro Uncertain significance ★ ⚠ same residue
ABCD1 p.Arg80_Leu82dup 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

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-arg85fs (accessed [today's date]).

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