Is ABCD1 p.Pro480= (c.1440C>A) pathogenic?

ABCD1 p.Pro480= (c.1440C>A) is classified Likely benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-21). Very rare (popmax 0.00033%); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Pro480= (c.1440C>A)?

ABCD1 p.Pro480= (c.1440C>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Pro480= (c.1440C>A) in the general population?

ABCD1 p.Pro480= (c.1440C>A) is very rare (popmax 0.00033%) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Pro480=

c.1440C>A · rs1557054320 · VCV1113831

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00033%)

Conditions

adrenoleukodystrophy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.714	pathogenic-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.34	GERP -2.1, phastCons 0.091
Overall
CADD	7.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00033%

Overall 0.00033% 4/1,211,962 alleles · very rare exomes 4/1,097,615 · genomes 0/114,347 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,349
Remaining individualsnot grpmax-eligible	0.0021%	47,655

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro480=
Coding: c.1440C>A
MANE Select: NM_000033
dbSNP: rs1557054320
Type: single nucleotide variant
Location: chrX:153737203 (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-pro480 (accessed [today's date]).

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