Is GDAP1 p.Asp129= (c.387C>T) pathogenic?

GDAP1 p.Asp129= (c.387C>T) is classified Likely benign in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-16). Very rare (popmax 0.000594%, nfe); Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.Asp129= (c.387C>T)?

GDAP1 p.Asp129= (c.387C>T) is associated with Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Asp129= (c.387C>T) in the general population?

GDAP1 p.Asp129= (c.387C>T) is very rare (popmax 0.000594%, nfe) (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.Asp129=

c.387C>T · rs1322630166 · VCV2199923

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

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 1.8	GERP 1.3, phastCons 1
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000594% European (non-Finnish) · 7/1,179,206 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,270 alleles · very rare exomes 8/1,460,972 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)grpmax	0.000594%	168,458

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp129=
Coding: c.387C>T
MANE Select: NM_018972
dbSNP: rs1322630166
Type: single nucleotide variant
Location: chr8:74360213 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 129: an α-helix

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.Asp129Asn Uncertain significance ★★ ⚠ same residue
GDAP1 p.Asp129His Uncertain significance ⚠ 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
GDAP1 p.Arg125Ter Pathogenic ★★ same condition
GDAP1 p.Arg161His Pathogenic/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-asp129 (accessed [today's date]).

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