Is GDAP1 p.Arg41= (c.123C>T) pathogenic?

GDAP1 p.Arg41= (c.123C>T) is classified Likely benign in GDAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-02). Very rare (popmax 0.00267%, afr); Associated with Charcot-Marie-Tooth disease.

What condition is associated with GDAP1 p.Arg41= (c.123C>T)?

GDAP1 p.Arg41= (c.123C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Arg41= (c.123C>T) in the general population?

GDAP1 p.Arg41= (c.123C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

GDAP1 p.Arg41=

c.123C>T · rs1395874165 · VCV917088

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Charcot-Marie-Tooth disease

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 1.7	GERP -3.6, phastCons 1
Overall
CADD	12.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,924 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,684 alleles · very rare exomes 1/1,461,500 · genomes 1/152,184 · 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.Arg41=
Coding: c.123C>T
MANE Select: NM_018972
dbSNP: rs1395874165
Type: single nucleotide variant
Location: chr8:74351279 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 41: the gst n-terminal domain; an α-helix

Full GDAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4A

Similar variants

GDAP1 p.Arg41Ser Uncertain significance ★ ⚠ same residue
GDAP1 p.Arg41Leu 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-arg41 (accessed [today's date]).

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