Is ABCD1 p.Pro734Arg (c.2201C>G) pathogenic?

ABCD1 p.Pro734Arg (c.2201C>G) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0732); Very rare (popmax 0.00754%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Pro734Arg (c.2201C>G)?

ABCD1 p.Pro734Arg (c.2201C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD1 p.Pro734Arg (c.2201C>G) in the general population?

ABCD1 p.Pro734Arg (c.2201C>G) is very rare (popmax 0.00754%, amr) (gnomAD).

What do computational predictors say about ABCD1 p.Pro734Arg (c.2201C>G)?

AlphaMissense predicts likely benign (score 0.0732) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro734Arg

c.2201C>G · rs368462762 · VCV2291665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00754%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0732	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -8.00	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 -0.045	GERP -1.4
Regional constraint	o/e 0.70	unconstrained · MANE · 242 bp · p 0.011 · regional, not allelic
Overall
CADD	3.85	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 0.00754% Admixed American · 3/39,802 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000342% 4/1,168,143 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00754%	13,267
African / African-American	0.00179%	56,014

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.Pro734Arg
Coding: c.2201C>G
MANE Select: NM_000033
dbSNP: rs368462762
Type: single nucleotide variant
Location: chrX:153743698 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 734: the 'required for homodimerization' region

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.Pro734Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCD1 p.Pro734= Likely benign ★ 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
ABCD1 p.Ser262Trp 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-pro734arg (accessed [today's date]).

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