Is ABCD1 p.Pro193Ala (c.577C>G) pathogenic?

ABCD1 p.Pro193Ala (c.577C>G) is classified Uncertain significance in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-16). AlphaMissense: likely benign (0.153); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Pro193Ala (c.577C>G)?

ABCD1 p.Pro193Ala (c.577C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD1 p.Pro193Ala (c.577C>G) in the general population?

ABCD1 p.Pro193Ala (c.577C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Pro193Ala (c.577C>G)?

AlphaMissense predicts likely benign (score 0.153) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro193Ala

c.577C>G · rs1557052424 · VCV2430754

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.153 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.153	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -6.47	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	19.38	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Pro193Ala
Coding: c.577C>G
MANE Select: NM_000033
dbSNP: rs1557052424
Type: single nucleotide variant
Location: chrX:153725843 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 193: the abc transmembrane type-1 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 p.Pro193Arg Pathogenic ★ same residue
ABCD1 p.Pro193= Likely benign ★ same residue
ABCD1 p.Pro193Ser Uncertain significance ⚠ same residue
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

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-pro193ala (accessed [today's date]).

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