Is GDAP1 p.Ala312fs (c.934del) pathogenic?

GDAP1 p.Ala312fs (c.934del) is classified Pathogenic in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.Ala312fs (c.934del)?

GDAP1 p.Ala312fs (c.934del) is associated with Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Ala312fs (c.934del) in the general population?

GDAP1 p.Ala312fs (c.934del) is ultra-rare (popmax 0.0165%, mid) (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.Ala312fs

c.934del · rs2536750938 · VCV2028969

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,614,204 alleles · ultra-rare exomes 1/1,461,886 · genomes 0/152,318 · 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.Ala312fs
Coding: c.934del
MANE Select: NM_018972
dbSNP: rs2536750938
Type: Deletion
Location: chr8:74364223 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB

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.Ala312Thr 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-ala312fs (accessed [today's date]).

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