Is ABCD1 p.Phe540= (c.1620C>T) pathogenic?

ABCD1 p.Phe540= (c.1620C>T) is classified Likely benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-03). Very rare (popmax 0.00867%, amr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Phe540= (c.1620C>T)?

ABCD1 p.Phe540= (c.1620C>T) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Phe540= (c.1620C>T) in the general population?

ABCD1 p.Phe540= (c.1620C>T) is very rare (popmax 0.00867%, amr) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Phe540=

c.1620C>T · rs782581290 · VCV1160735

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00867%, amr)

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.19	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 1
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00867% Admixed American · 4/46,135 alleles

Filtering AF 0.00292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.000546% 6/1,097,951 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00867%	11,534
European (non-Finnish)	0.000223%	447,816

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.Phe540=
Coding: c.1620C>T
MANE Select: NM_000033
dbSNP: rs782581290
Type: single nucleotide variant
Location: chrX:153740223 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 540: a UniProt-annotated variant site (in ald); a β-strand; 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.Phe540Leu Uncertain significance ★ ⚠ same residue
ABCD1 p.Phe540Cys Likely 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

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-phe540 (accessed [today's date]).

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