Is GDAP1 p.Arg310fs (c.928del) pathogenic?

GDAP1 p.Arg310fs (c.928del) is classified Uncertain significance in GDAP1 (ClinVar, Single submitter, 3 submitters; last evaluated 2026-02-06). Very rare (popmax 0.00381%, nfe); Associated with Charcot-Marie-Tooth disease axonal type 2K.

What condition is associated with GDAP1 p.Arg310fs (c.928del)?

GDAP1 p.Arg310fs (c.928del) is associated with Charcot-Marie-Tooth disease axonal type 2K, Charcot-Marie-Tooth disease (ClinVar).

How common is GDAP1 p.Arg310fs (c.928del) in the general population?

GDAP1 p.Arg310fs (c.928del) is very rare (popmax 0.00381%, nfe) (gnomAD).

GDAP1 p.Arg310fs

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.928del · rs1586807541 · VCV637555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

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 7.9	GERP 2.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00381% European (non-Finnish) · 45/1,180,022 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00285% 46/1,614,186 alleles · very rare exomes 46/1,461,878 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,223
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Arg310fs
Coding: c.928del
MANE Select: NM_018972
dbSNP: rs1586807541
Type: Deletion
Location: chr8:74364217 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 310: a UniProt-annotated variant site (in cmt2rv; abolishes mitochondrial fission); a UniProt-annotated variant site (in cmt2k; recessive form)

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

Also linked: Charcot-Marie-Tooth disease

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GDAP1 p.Arg310Gln Pathogenic/Likely pathogenic ★★ ⚠ 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.Tyr279_Tyr280insTer Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Ala264fs Likely pathogenic ★ same condition
GDAP1 p.Arg310Trp Pathogenic ★ ⚠ same residue
GDAP1 p.Asp134fs 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-arg310fs (accessed [today's date]).

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