Is ABCD1 p.Thr693= (c.2079G>A) pathogenic?

ABCD1 p.Thr693= (c.2079G>A) is classified Likely benign in ABCD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-22). Very rare (popmax 0.00698%, afr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Thr693= (c.2079G>A)?

ABCD1 p.Thr693= (c.2079G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Thr693= (c.2079G>A) in the general population?

ABCD1 p.Thr693= (c.2079G>A) is very rare (popmax 0.00698%, afr) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Thr693=

c.2079G>A · rs781935761 · VCV706672

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00698%, afr)

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 -20	GERP -3.5
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00698% African / African-American · 4/57,308 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00367% 44/1,198,926 alleles · very rare exomes 35/1,086,006 · genomes 9/112,920 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00698%	14,327
Remaining individualsnot grpmax-eligible	0.00425%	23,526
European (non-Finnish)	0.00382%	26,180
South Asian	0.00362%	27,633
East Asian	0.003%	33,323
Admixed American	0.00223%	44,794

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.Thr693=
Coding: c.2079G>A
MANE Select: NM_000033
dbSNP: rs781935761
Type: single nucleotide variant
Location: chrX:153743576 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 693: the 'required for homodimerization' region; 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.Thr693Met Uncertain significance ★★ ⚠ same residue
ABCD1 p.Thr693Pro 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-thr693 (accessed [today's date]).

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