Is ABCD1 p.Pro243= (c.729C>G) pathogenic?

ABCD1 p.Pro243= (c.729C>G) is classified Benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-18). Very rare (popmax 0.000895%, nfe); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Pro243= (c.729C>G)?

ABCD1 p.Pro243= (c.729C>G) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Pro243= (c.729C>G) in the general population?

ABCD1 p.Pro243= (c.729C>G) is very rare (popmax 0.000895%, 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.Pro243=

c.729C>G · rs1557052503 · VCV1609160

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000895%, 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 0.11	GERP -3.4, phastCons 0.92
Overall
CADD	6.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000895% European (non-Finnish) · 8/894,342 alleles

Filtering AF 0.000385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000731% 8/1,094,626 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.Pro243=
Coding: c.729C>G
MANE Select: NM_000033
dbSNP: rs1557052503
Type: single nucleotide variant
Location: chrX:153725995 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 243: an α-helix; the abc transmembrane type-1 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.Pro243Arg Uncertain significance ★ ⚠ 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-pro243 (accessed [today's date]).

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