Is ABCD1 p.Arg617Cys (c.1849C>T) pathogenic?

ABCD1 p.Arg617Cys (c.1849C>T) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.9335); Very rare (popmax 0.000113%, nfe); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Arg617Cys (c.1849C>T)?

ABCD1 p.Arg617Cys (c.1849C>T) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg617Cys (c.1849C>T) in the general population?

ABCD1 p.Arg617Cys (c.1849C>T) is very rare (popmax 0.000113%, nfe) (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.Arg617Cys (c.1849C>T)?

AlphaMissense predicts likely pathogenic (score 0.9335) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg617Cys

c.1849C>T · rs4010613 · VCV11313

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.9335 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
AlphaMissense	0.9335	likely pathogenic ✓ concordant with ClinVar
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -13.42	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 4.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	32.0	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 0.000113% European (non-Finnish) · 1/887,932 alleles

Overall 9.24e-05% 1/1,082,491 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.Arg617Cys
Coding: c.1849C>T
MANE Select: NM_000033
dbSNP: rs4010613
Type: single nucleotide variant
Location: chrX:153743055 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 617: a UniProt-annotated variant site (in ald; ald-type and asymptomatic); a UniProt-annotated variant site (in ald; ado and amn-types with cerebral involvement); 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.Arg617His Pathogenic ★★ same residue
ABCD1 p.Arg617Leu Uncertain significance ★ ⚠ same residue
ABCD1 p.Arg617Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCD1 p.Arg617fs Pathogenic ★ same residue
ABCD1 p.Arg617Gly 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

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-arg617cys (accessed [today's date]).

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