Is GDAP1 p.Ser57fs (c.167dup) pathogenic?

GDAP1 p.Ser57fs (c.167dup) is classified Pathogenic in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-26). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.Ser57fs (c.167dup)?

GDAP1 p.Ser57fs (c.167dup) is associated with Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Ser57fs (c.167dup) in the general population?

GDAP1 p.Ser57fs (c.167dup) is no gnomAD frequency available for this variant (gnomAD).

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.Ser57fs

c.167dup · rs2536724780 · VCV2730373

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GDAP1
Protein: p.Ser57fs
Coding: c.167dup
MANE Select: NM_018972
dbSNP: rs2536724780
Type: Duplication
Location: chr8:74351322 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 57: the gst n-terminal domain

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

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GDAP1 p.Ser57Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
GDAP1 p.Lys207fs Pathogenic ★ same condition
GDAP1 p.Thr323fs Likely pathogenic ★ same condition
GDAP1 p.Arg341fs Conflicting classifications of pathogenicity ★ same condition
GDAP1 c.484+6_484+19dup Likely benign ★ same condition
GDAP1 c.579+13_579+14dup Likely benign ★ same condition
GDAP1 c.311-1G>A Pathogenic/Likely pathogenic ★★ same condition
GDAP1 c.579+1G>A 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-ser57fs (accessed [today's date]).

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