Is ABCD1 p.Gly486Arg (c.1456G>A) pathogenic?

ABCD1 p.Gly486Arg (c.1456G>A) is classified Benign/Likely benign in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-25). AlphaMissense: likely pathogenic (0.6126); Very rare (popmax 0.000782%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Gly486Arg (c.1456G>A)?

ABCD1 p.Gly486Arg (c.1456G>A) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Gly486Arg (c.1456G>A) in the general population?

ABCD1 p.Gly486Arg (c.1456G>A) is very rare (popmax 0.000782%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Gly486Arg (c.1456G>A)?

AlphaMissense predicts likely pathogenic (score 0.6126) — an in-silico prediction, not a clinical call.

ABCD1 p.Gly486Arg

c.1456G>A · rs782242003 · VCV1170323

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6126 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000782%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6126	likely pathogenic
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -10.57	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 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	24.9	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 0.000782% European (non-Finnish) · 7/895,595 alleles

Filtering AF 0.000325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000638% 7/1,097,310 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.Gly486Arg
Coding: c.1456G>A
MANE Select: NM_000033
dbSNP: rs782242003
Type: single nucleotide variant
Location: chrX:153737219 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 486: a β-strand; the abc transporter domain

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.Gly486= Likely benign ★ 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
ABCD1 c.1866-1G>C Likely pathogenic ★★ same condition
ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
ABCD1 c.901-1G>A 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-gly486arg (accessed [today's date]).

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