Is ABCD1 p.Ser58Cys (c.173C>G) pathogenic?

ABCD1 p.Ser58Cys (c.173C>G) is classified Likely benign in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-17). AlphaMissense: likely benign (0.0859); Ultra-rare (popmax 0.0159%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Ser58Cys (c.173C>G)?

ABCD1 p.Ser58Cys (c.173C>G) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ser58Cys (c.173C>G) in the general population?

ABCD1 p.Ser58Cys (c.173C>G) is ultra-rare (popmax 0.0159%, eas) (gnomAD).

What do computational predictors say about ABCD1 p.Ser58Cys (c.173C>G)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

ABCD1 p.Ser58Cys

c.173C>G · rs781943986 · VCV2060249

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -2.7
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	13.67	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 0.0159% East Asian · 5/31,479 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00406%

Overall 0.000689% 8/1,160,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,296
Remaining individualsnot grpmax-eligible	0.0044%	22,721
Admixed American	0.00254%	39,301

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.Ser58Cys
Coding: c.173C>G
MANE Select: NM_000033
dbSNP: rs781943986
Type: single nucleotide variant
Location: chrX:153725439 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB

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

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Ser58= Likely benign ★ same residue
ABCD1 p.Ser58Phe Likely benign ★ 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-ser58cys (accessed [today's date]).

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