Is ABCD1 p.Arg163His (c.488G>A) pathogenic?

ABCD1 p.Arg163His (c.488G>A) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-18). AlphaMissense: likely pathogenic (0.7365); Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Arg163His (c.488G>A)?

ABCD1 p.Arg163His (c.488G>A) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg163His (c.488G>A) in the general population?

ABCD1 p.Arg163His (c.488G>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Arg163His (c.488G>A)?

AlphaMissense predicts likely pathogenic (score 0.7365) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg163His

c.488G>A · rs1057517954 · VCV372736

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.7365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7365	likely pathogenic ✓ concordant with ClinVar
REVEL	0.966	strongly pathogenic-leaning
SaProt	LLR -11.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,659 alleles

Overall 9.11e-05% 1/1,097,568 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.Arg163His
Coding: c.488G>A
MANE Select: NM_000033
dbSNP: rs1057517954
Type: single nucleotide variant
Location: chrX:153725754 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 163: an α-helix; a UniProt-annotated variant site (in ald); the abc transmembrane type-1 domain; the 'interaction with pex19' region

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Arg163Cys Pathogenic/Likely pathogenic ★★ same residue
ABCD1 p.Arg163Gly Likely pathogenic ★★ same residue
ABCD1 p.Arg163Leu Likely pathogenic ★ same residue
ABCD1 p.Arg163Ser Likely pathogenic ★ same residue
ABCD1 p.Arg163= Likely benign ★ same residue
ABCD1 p.Arg163fs Pathogenic ★ same residue
ABCD1 p.Arg163del Uncertain significance ★ same residue
ABCD1 p.Arg163Pro Pathogenic ★ same residue

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-arg163his (accessed [today's date]).

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