Is ABCD1 p.Leu516= (c.1548G>A) pathogenic?

ABCD1 p.Leu516= (c.1548G>A) is classified Benign in ABCD1 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). Common (popmax 15%, sas) — too common for a highly-penetrant pathogenic allele; Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Leu516= (c.1548G>A)?

ABCD1 p.Leu516= (c.1548G>A) is associated with adrenoleukodystrophy (ClinVar).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Leu516=

Q: How common is ABCD1 p.Leu516= (c.1548G>A) in the general population?

ABCD1 p.Leu516= (c.1548G>A) is common (popmax 15%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1548G>A · rs41314153 · VCV92316

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Common

common (popmax 15%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.249	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.042	GERP -3.8, phastCons 0.61
Overall
CADD	4.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15% South Asian · 8,533/56,796 alleles

Filtering AF 14.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 10.8% 130,426/1,209,397 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	15%	7
European (non-Finnish)	11.6%	9
Finnishnot grpmax-eligible	10.6%	9
Remaining individualsnot grpmax-eligible	10%	10
Middle Eastern	8.11%	12
Ashkenazi Jewishnot grpmax-eligible	6.74%	15
Admixed American	5.49%	18
East Asian	5.25%	19
African / African-American	4.5%	22
Amishnot grpmax-eligible	2.18%	46

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.Leu516=
Coding: c.1548G>A
MANE Select: NM_000033
dbSNP: rs41314153
Type: single nucleotide variant
Location: chrX:153740151 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 516: a UniProt-annotated variant site (in ald); an α-helix; 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.Leu516Pro 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
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-leu516 (accessed [today's date]).

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