Is ABCD1 p.Pro737Ser (c.2209C>T) pathogenic?

ABCD1 p.Pro737Ser (c.2209C>T) is classified Uncertain significance in ABCD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0683); Very rare (popmax 0.00252%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Pro737Ser (c.2209C>T)?

ABCD1 p.Pro737Ser (c.2209C>T) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Pro737Ser (c.2209C>T) in the general population?

ABCD1 p.Pro737Ser (c.2209C>T) is very rare (popmax 0.00252%, amr) (gnomAD).

What do computational predictors say about ABCD1 p.Pro737Ser (c.2209C>T)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro737Ser

c.2209C>T · rs1290462360 · VCV624452

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00252%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.15	GERP -0.22, phastCons 0.24
Regional constraint	o/e 0.70	unconstrained · MANE · 242 bp · p 0.011 · regional, not allelic
Overall
CADD	2.353	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00252% Admixed American · 1/39,660 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000257% 3/1,166,547 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00252%	39,660
European (non-Finnish)	0.000228%	438,022

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.Pro737Ser
Coding: c.2209C>T
dbSNP: rs1290462360
Type: single nucleotide variant
Location: chrX:153743706 (GRCh38)

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

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-pro737ser (accessed [today's date]).

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