Is ABCD1 p.Leu82= (c.244C>T) pathogenic?

ABCD1 p.Leu82= (c.244C>T) is classified Likely benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). Very rare (popmax 0.000115%, nfe); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Leu82= (c.244C>T)?

ABCD1 p.Leu82= (c.244C>T) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Leu82= (c.244C>T) in the general population?

ABCD1 p.Leu82= (c.244C>T) is very rare (popmax 0.000115%, nfe) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Leu82=

c.244C>T · rs2091704763 · VCV2862070

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000115%, nfe)

Conditions

adrenoleukodystrophy

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 4.8	GERP 0.3, phastCons 1
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000115% European (non-Finnish) · 1/871,913 alleles

Overall 9.52e-05% 1/1,050,412 alleles · very rare

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.Leu82=
Coding: c.244C>T
MANE Select: NM_000033
dbSNP: rs2091704763
Type: single nucleotide variant
Location: chrX:153725510 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 82: an α-helix; the 'interaction with pex19' region; the 'pex19 binding site and required for peroxisomal targeting' region

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.Leu82fs Pathogenic ★ 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
ABCD1 c.901-1G>A 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-leu82 (accessed [today's date]).

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