Is ABCD1 p.Gln718Pro (c.2153A>C) pathogenic?

ABCD1 p.Gln718Pro (c.2153A>C) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.4521); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Gln718Pro (c.2153A>C)?

ABCD1 p.Gln718Pro (c.2153A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD1 p.Gln718Pro (c.2153A>C) in the general population?

ABCD1 p.Gln718Pro (c.2153A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Gln718Pro (c.2153A>C)?

AlphaMissense predicts ambiguous (score 0.4521) — an in-silico prediction, not a clinical call.

ABCD1 p.Gln718Pro

c.2153A>C · VCV4564388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4521 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4521	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -13.07	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 0.78, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 242 bp · p 0.011 · regional, not allelic
Overall
CADD	21.0	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.Gln718Pro
Coding: c.2153A>C
MANE Select: NM_000033
Type: single nucleotide variant
Location: chrX:153743650 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 718: the 'required for homodimerization' region; an α-helix

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-gln718pro (accessed [today's date]).

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