Is GDAP1 p.Arg341fs (c.1019dup) pathogenic?

GDAP1 p.Arg341fs (c.1019dup) is classified Conflicting classifications of pathogenicity in GDAP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-06). Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GDAP1 p.Arg341fs (c.1019dup)?

GDAP1 p.Arg341fs (c.1019dup) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease axonal type 2K (ClinVar).

How common is GDAP1 p.Arg341fs (c.1019dup) in the general population?

GDAP1 p.Arg341fs (c.1019dup) is very rare (popmax 0.00161%, nfe) (gnomAD).

GDAP1 p.Arg341fs

c.1019dup · rs756461496 · VCV406140

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

Inborn genetic diseases

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 2.7	GERP 2.6, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,944 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,613,896 alleles · very rare exomes 16/1,461,796 · genomes 3/152,100 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GDAP1
Protein: p.Arg341fs
Coding: c.1019dup
MANE Select: NM_018972
dbSNP: rs756461496
Type: Duplication
Location: chr8:74364305 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 341: the 'required for mitochondrial localization' region

Full GDAP1 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

Also linked: Charcot-Marie-Tooth disease type 4A Charcot-Marie-Tooth disease axonal type 2K Charcot-Marie-Tooth disease

Similar variants

GDAP1 p.Lys207fs Pathogenic ★ same condition
GDAP1 p.Ser57fs Pathogenic ★ same condition
GDAP1 p.Thr323fs Likely pathogenic ★ same condition
GDAP1 p.Tyr117fs Pathogenic ★ same condition
GDAP1 c.484+6_484+19dup Likely benign ★ same condition
GDAP1 c.579+13_579+14dup Likely benign ★ same condition
GDAP1 p.Phe289fs Uncertain significance same condition
GDAP1 p.Ser34fs 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/gdap1-p-arg341fs (accessed [today's date]).

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