Is GDAP1 p.Ala264fs (c.791del) pathogenic?

GDAP1 p.Ala264fs (c.791del) is classified Likely pathogenic in GDAP1 (ClinVar, Single submitter, 1 submitter). Associated with Charcot-Marie-Tooth disease axonal type 2K.

What condition is associated with GDAP1 p.Ala264fs (c.791del)?

GDAP1 p.Ala264fs (c.791del) is associated with Charcot-Marie-Tooth disease axonal type 2K (ClinVar).

GDAP1 p.Ala264fs

Q: How is Autosomal recessive Charcot-Marie-Tooth disease with hoarseness inherited?

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

c.791del · VCV4532247

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Charcot-Marie-Tooth disease axonal type 2K

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1

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

Variant & gene context

Gene: GDAP1
Protein: p.Ala264fs
Coding: c.791del
MANE Select: NM_018972
Type: Deletion
Location: chr8:74364081 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 264: the gst c-terminal domain

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

Disease context

Charcot-Marie-Tooth disease axonal type 2K — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive Charcot-Marie-Tooth disease with hoarseness (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GDAP1 p.Glu168fs Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Met1fs Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Tyr279_Tyr280insTer Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Asp134fs Pathogenic ★ same condition
GDAP1 p.Ile186fs Pathogenic ★ same condition
GDAP1 p.Lys193fs Pathogenic ★ same condition
GDAP1 p.Lys47fs Pathogenic ★ same condition
GDAP1 c.310+6del Conflicting classifications of pathogenicity ★ 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-ala264fs (accessed [today's date]).

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