Is ABCD1 p.Val419= (c.1257G>A) pathogenic?

ABCD1 p.Val419= (c.1257G>A) is classified Likely benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Very rare (popmax 0.00527%, sas); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Val419= (c.1257G>A)?

ABCD1 p.Val419= (c.1257G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Val419= (c.1257G>A) in the general population?

ABCD1 p.Val419= (c.1257G>A) is very rare (popmax 0.00527%, sas) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ABCD1 p.Val419=

c.1257G>A · rs1603234541 · VCV794254

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00527%, sas)

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.133	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -2.5
Overall
CADD	0.845	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00527% South Asian · 3/56,902 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000688%

Overall 0.000496% 6/1,210,813 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00527%	18,967
Remaining individualsnot grpmax-eligible	0.0021%	47,610
European (non-Finnish)	0.000223%	447,686

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.Val419=
Coding: c.1257G>A
MANE Select: NM_000033
dbSNP: rs1603234541
Type: single nucleotide variant
Location: chrX:153736377 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 419: an α-helix

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.Val419Leu Uncertain significance ★★ ⚠ same residue
ABCD1 p.Val419Ala Pathogenic ★ same residue
ABCD1 p.Val419Gly Uncertain significance ★ ⚠ 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

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-val419 (accessed [today's date]).

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