Is ABCD1 p.Arg389Ser (c.1165C>A) pathogenic?

ABCD1 p.Arg389Ser (c.1165C>A) is classified Likely pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-08). AlphaMissense: likely pathogenic (0.9692); Absent from gnomAD v4.1; Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Arg389Ser (c.1165C>A)?

ABCD1 p.Arg389Ser (c.1165C>A) is associated with ABCD1-related disorder (ClinVar).

How common is ABCD1 p.Arg389Ser (c.1165C>A) in the general population?

ABCD1 p.Arg389Ser (c.1165C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Arg389Ser (c.1165C>A)?

AlphaMissense predicts likely pathogenic (score 0.9692) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg389Ser

c.1165C>A · VCV4953341

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9692 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9692	likely pathogenic ✓ concordant with ClinVar
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Arg389Ser
Coding: c.1165C>A
MANE Select: NM_000033
Type: single nucleotide variant
Location: chrX:153736195 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 389: a β-strand; a UniProt-annotated variant site (in ald; amn-type); a UniProt-annotated variant site (in ald; does not affect protein stability, homo- and heterodimerization with abcd2 and abcd3)

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

Disease context

ABCD1-related disorder

Similar variants

ABCD1 p.Arg389= Likely benign ★ same residue
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
ABCD1 c.901-5C>A Likely pathogenic ★★ same condition
ABCD1 p.Arg104His Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg152Cys Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg163Cys Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg280Cys Pathogenic/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-arg389ser (accessed [today's date]).

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