Is GDAP1 p.Cys240= (c.720C>T) pathogenic?

GDAP1 p.Cys240= (c.720C>T) is classified Likely benign in GDAP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-16). Ultra-rare (popmax 0.0134%, eas); Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.Cys240= (c.720C>T)?

GDAP1 p.Cys240= (c.720C>T) is associated with Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease (ClinVar).

How common is GDAP1 p.Cys240= (c.720C>T) in the general population?

GDAP1 p.Cys240= (c.720C>T) is ultra-rare (popmax 0.0134%, eas) (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.Cys240=

c.720C>T · rs367790253 · VCV514656

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Charcot-Marie-Tooth disease type 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -5.5
Overall
CADD	6.618	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00709%

Overall 0.0075% 121/1,613,588 alleles · ultra-rare exomes 113/1,461,482 · genomes 8/152,106 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
European (non-Finnish)	0.00907%	11,025
Remaining individualsnot grpmax-eligible	0.008%	12,496
African / African-American	0.00267%	37,445
South Asian	0.0011%	91,074

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.Cys240=
Coding: c.720C>T
MANE Select: NM_018972
dbSNP: rs367790253
Type: single nucleotide variant
Location: chr8:74364010 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 240: the gst c-terminal domain; a β-strand

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

Also linked: Charcot-Marie-Tooth disease

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GDAP1 p.Cys240Ser Uncertain significance ★★ ⚠ same residue
GDAP1 p.Cys240Ter Likely pathogenic ★ same residue
GDAP1 p.Cys240Phe Uncertain significance ★ ⚠ same residue
GDAP1 p.Cys240Tyr Conflicting classifications of pathogenicity ⚠ same residue
GDAP1 c.311-1G>A Pathogenic/Likely pathogenic ★★ same condition
GDAP1 c.579+1G>A Pathogenic ★★ same condition
GDAP1 c.694+1G>A Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Arg120Trp 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-cys240 (accessed [today's date]).

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