Is GDAP1 p.Asp134fs (c.400del) pathogenic?

GDAP1 p.Asp134fs (c.400del) is classified Pathogenic in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Associated with Charcot-Marie-Tooth disease type 4A.

How is Charcot-Marie-Tooth disease type 4A inherited?

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

GDAP1 p.Asp134fs

Q: What condition is associated with GDAP1 p.Asp134fs (c.400del)?

GDAP1 p.Asp134fs (c.400del) is associated with Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive, Charcot-Marie-Tooth disease axonal type 2K (ClinVar).

c.400del · VCV3595879

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Charcot-Marie-Tooth disease type 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: GDAP1
Protein: p.Asp134fs
Coding: c.400del
MANE Select: NM_018972
Type: Deletion
Location: chr8:74360225 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 134: an α-helix

Full GDAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive Charcot-Marie-Tooth disease axonal type 2K Charcot-Marie-Tooth disease recessive intermediate A

For Charcot-Marie-Tooth disease type 4A (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GDAP1 p.Asp134Tyr Uncertain significance ★ ⚠ same residue
GDAP1 p.Glu168fs Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Met1fs Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Phe263fs Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Pro179fs Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Tyr279_Tyr280insTer Pathogenic/Likely pathogenic ★★ same condition
GDAP1 c.311-1790_408del Likely pathogenic ★ same condition
GDAP1 c.485-2del 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/gdap1-p-asp134fs (accessed [today's date]).

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