Is ABCD1 p.Pro536Ser (c.1606C>T) pathogenic?

ABCD1 p.Pro536Ser (c.1606C>T) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.1544); Very rare (popmax 0.001%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Pro536Ser (c.1606C>T)?

ABCD1 p.Pro536Ser (c.1606C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD1 p.Pro536Ser (c.1606C>T) in the general population?

ABCD1 p.Pro536Ser (c.1606C>T) is very rare (popmax 0.001%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Pro536Ser (c.1606C>T)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro536Ser

c.1606C>T · rs2522297458 · VCV2335912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.001%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.681	pathogenic-leaning
SaProt	LLR -6.96	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	20.3	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 0.001% European (non-Finnish) · 9/895,590 alleles

Filtering AF 0.000473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000342%

Overall 0.00082% 9/1,098,026 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.Pro536Ser
Coding: c.1606C>T
MANE Select: NM_000033
dbSNP: rs2522297458
Type: single nucleotide variant
Location: chrX:153740209 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 536: an α-helix; 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

Similar variants

ABCD1 c.1635-2A>G Pathogenic ★★ same condition
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg163His Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg189Trp Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Gly266Arg Pathogenic ★★ ⚠ same condition
ABCD1 p.Ser262Trp Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Tyr296Cys Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Ala238Thr Uncertain significance ★★ ⚠ 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-pro536ser (accessed [today's date]).

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