Is ABCD1 p.Thr386Ala (c.1156A>G) pathogenic?

ABCD1 p.Thr386Ala (c.1156A>G) is classified Uncertain significance in ABCD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.2442); Very rare (popmax 0.000112%, nfe); Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Thr386Ala (c.1156A>G)?

ABCD1 p.Thr386Ala (c.1156A>G) is associated with ABCD1-related disorder (ClinVar).

How common is ABCD1 p.Thr386Ala (c.1156A>G) in the general population?

ABCD1 p.Thr386Ala (c.1156A>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Thr386Ala (c.1156A>G)?

AlphaMissense predicts likely benign (score 0.2442) — an in-silico prediction, not a clinical call.

ABCD1 p.Thr386Ala

c.1156A>G · rs1205548762 · VCV3054663

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2442	likely benign
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -10.29	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	23.3	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) · 1/895,317 alleles

Overall 0.00089% 1/112,298 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.Thr386Ala
Coding: c.1156A>G
MANE Select: NM_000033
dbSNP: rs1205548762
Type: single nucleotide variant
Location: chrX:153736186 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 386: an α-helix; the abc transmembrane type-1 domain

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

Disease context

ABCD1-related disorder

Similar variants

ABCD1 p.Thr386Pro Uncertain significance ★★ ⚠ same residue
ABCD1 p.Thr386Ser Uncertain significance ★ ⚠ same residue
ABCD1 p.Thr386= Likely benign ★ same residue
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
ABCD1 c.901-5C>A Likely pathogenic ★★ same condition
ABCD1 p.Arg104His Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg152Cys 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-thr386ala (accessed [today's date]).

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