Is ABCD1 p.Pro560Leu (c.1679C>T) pathogenic?

ABCD1 p.Pro560Leu (c.1679C>T) is classified Pathogenic in ABCD1 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2025-11-13). AlphaMissense: likely pathogenic (0.9559); Very rare (popmax 0.000112%, nfe); Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Pro560Leu (c.1679C>T)?

ABCD1 p.Pro560Leu (c.1679C>T) is associated with ABCD1-related disorder, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Pro560Leu (c.1679C>T) in the general population?

ABCD1 p.Pro560Leu (c.1679C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Pro560Leu (c.1679C>T)?

AlphaMissense predicts likely pathogenic (score 0.9559) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro560Leu

c.1679C>T · rs398123105 · VCV92320

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely pathogenic

0.9559 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9559	likely pathogenic ✓ concordant with ClinVar
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -16.22	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	26.4	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) · 1/895,290 alleles

Overall 9.12e-05% 1/1,096,432 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.Pro560Leu
Coding: c.1679C>T
MANE Select: NM_000033
dbSNP: rs398123105
Type: single nucleotide variant
Location: chrX:153740618 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 560: a UniProt-annotated variant site (in ald; cald-type); a UniProt-annotated variant site (in ald; amn and almd-types); a UniProt-annotated variant site (in ald); a turn; the abc transporter domain

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

Disease context

ABCD1-related disorder

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Pro560= Likely benign ★★ same residue
ABCD1 p.Pro560Arg Likely pathogenic ★ same residue
ABCD1 p.Pro560Ser Likely pathogenic ★ same residue
ABCD1 p.Pro560Thr Likely 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
ABCD1 c.1866-10G>A 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-pro560leu (accessed [today's date]).

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