Is ABCD4 p.His586Asp (c.1756C>G) pathogenic?

ABCD4 p.His586Asp (c.1756C>G) is classified Uncertain significance in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-12). AlphaMissense: likely pathogenic (0.9914); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD4 p.His586Asp (c.1756C>G)?

ABCD4 p.His586Asp (c.1756C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD4 p.His586Asp (c.1756C>G) in the general population?

ABCD4 p.His586Asp (c.1756C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD4 p.His586Asp (c.1756C>G)?

AlphaMissense predicts likely pathogenic (score 0.9914) — an in-silico prediction, not a clinical call.

ABCD4 p.His586Asp

c.1756C>G · rs371791289 · VCV2228673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9914 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9914	likely pathogenic · top 3% in ABCD4
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -16.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.79 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ABCD4
Protein: p.His586Asp
Coding: c.1756C>G
MANE Select: NM_005050
dbSNP: rs371791289
Type: single nucleotide variant
Location: chr14:74286526 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB
Residue 586: the abc transporter domain

Full ABCD4 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

ABCD4 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg252Gly Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg391Gln Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg442Gln Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gln215Arg Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gln446Arg Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gly566Ser Uncertain significance ★★ ⚠ same condition
ABCD4 p.Leu157Val 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/abcd4-p-his586asp (accessed [today's date]).

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