Is ABCD1 p.Pro730Arg (c.2189C>G) pathogenic?

ABCD1 p.Pro730Arg (c.2189C>G) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00499%, amr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Pro730Arg (c.2189C>G)?

ABCD1 p.Pro730Arg (c.2189C>G) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Pro730Arg (c.2189C>G) in the general population?

ABCD1 p.Pro730Arg (c.2189C>G) is very rare (popmax 0.00499%, amr) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

What do computational predictors say about ABCD1 p.Pro730Arg (c.2189C>G)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro730Arg

c.2189C>G · VCV3707000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00499%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

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
AlphaMissense	0.0999	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2	GERP -0.85
Regional constraint	o/e 0.70	unconstrained · MANE · 242 bp · p 0.011 · regional, not allelic
Overall
CADD	6.139	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00499% Admixed American · 2/40,108 alleles

Filtering AF 0.000826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000576%

Overall 0.00128% 15/1,169,981 alleles · very rare exomes 14/1,058,068 · genomes 1/111,913 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00499%	20,054
South Asian	0.00189%	52,844
European (non-Finnish)	0.00137%	73,068

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.Pro730Arg
Coding: c.2189C>G
MANE Select: NM_000033
Type: single nucleotide variant
Location: chrX:153743686 (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-pro730arg (accessed [today's date]).

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