Is ABCD1 p.Asp638= (c.1914C>T) pathogenic?

ABCD1 p.Asp638= (c.1914C>T) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0305%, mid); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Asp638= (c.1914C>T)?

ABCD1 p.Asp638= (c.1914C>T) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Asp638= (c.1914C>T) in the general population?

ABCD1 p.Asp638= (c.1914C>T) is ultra-rare (popmax 0.0305%, mid) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Asp638=

c.1914C>T · rs199723613 · VCV528350

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0305%, mid)

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.2	GERP -2.1
Overall
CADD	2.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0305% Middle Eastern · 1/3,277 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00935%

Overall 0.00978% 118/1,206,150 alleles · ultra-rare exomes 111/1,093,401 · genomes 7/112,749 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0305%	3,277
Remaining individualsnot grpmax-eligible	0.0169%	5,925
European (non-Finnish)	0.012%	8,353
South Asian	0.00178%	56,086
African / African-American	0.00174%	57,341

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.Asp638=
Coding: c.1914C>T
MANE Select: NM_000033
dbSNP: rs199723613
Type: single nucleotide variant
Location: chrX:153743269 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 638: 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.Asp638Asn Uncertain significance ★★ ⚠ same residue
ABCD1 p.Asp638Ala 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
ABCD1 c.1866-2A>T 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-asp638 (accessed [today's date]).

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