Is ABCD1 p.Glu408= (c.1224G>A) pathogenic?

ABCD1 p.Glu408= (c.1224G>A) is classified Pathogenic in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-20). Absent from gnomAD v4.1; Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Glu408= (c.1224G>A)?

ABCD1 p.Glu408= (c.1224G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Glu408= (c.1224G>A) in the general population?

ABCD1 p.Glu408= (c.1224G>A) 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.Glu408=

c.1224G>A · rs2148395507 · VCV1455740

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.171	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.76	loss · gain 0.09 · independent
Constraint at this position
Conservation	phyloP 9	GERP 1.6, phastCons 1
Overall
CADD	19.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Glu408=
Coding: c.1224G>A
dbSNP: rs2148395507
Type: single nucleotide variant
Location: chrX:153736254 (GRCh38)

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)

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-glu408 (accessed [today's date]).

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