Is DCAF8 p.Ser130del (c.385TCA[1]) pathogenic?

DCAF8 p.Ser130del (c.385TCA[1]) is classified Uncertain significance in DCAF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). Associated with giant axonal neuropathy 2.

What condition is associated with DCAF8 p.Ser130del (c.385TCA[1])?

DCAF8 p.Ser130del (c.385TCA[1]) is associated with giant axonal neuropathy 2 (ClinVar).

DCAF8 p.Ser130del

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.385TCA[1] · VCV4819653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

giant axonal neuropathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1

Variant & gene context

Gene: DCAF8
Protein: p.Ser130del
Coding: c.385TCA[1]
MANE Select: NM_015726
Type: Microsatellite
Location: chr1:160240030 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB
Residue 130: a modified residue (phosphoserine); the 'disordered' region

Full DCAF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

giant axonal neuropathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

DCAF8 p.Arg122Trp Uncertain significance ★★ ⚠ same condition
DCAF8 p.Lys274= Benign/Likely benign ★★ same condition
DCAF8 p.Arg317Cys Likely pathogenic ★ same condition
DCAF8 p.Arg151Cys Uncertain significance ★ ⚠ same condition
DCAF8 p.Arg278His Uncertain significance ★ ⚠ same condition
DCAF8 p.Gly475Arg Uncertain significance ★ same condition
DCAF8 p.Ser576Phe Uncertain significance ★ ⚠ same condition
DCAF8 p.Glu111_Glu112del Benign/Likely benign ★★ same type

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/dcaf8-p-ser130del (accessed [today's date]).

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