Is GDAP1 p.Arg282= (c.846T>A) pathogenic?

GDAP1 p.Arg282= (c.846T>A) is classified Likely benign in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-20). Very rare (popmax 0.00167%, amr); Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.Arg282= (c.846T>A)?

GDAP1 p.Arg282= (c.846T>A) is associated with Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Arg282= (c.846T>A) in the general population?

GDAP1 p.Arg282= (c.846T>A) is very rare (popmax 0.00167%, amr) (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.Arg282=

c.846T>A · rs751766713 · VCV1088441

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 1.5	GERP -1.2, phastCons 1
Overall
CADD	10.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,614,182 alleles · very rare exomes 17/1,461,882 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,028
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,028
European (non-Finnish)	0.00119%	84,289

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.Arg282=
Coding: c.846T>A
MANE Select: NM_018972
dbSNP: rs751766713
Type: single nucleotide variant
Location: chr8:74364136 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 282: a UniProt-annotated variant site (in cmtria; no effect on mitochondrial localization but impairment in the ability to induce mitochondrial fragmentation); a UniProt-annotated variant site (in cmt2k; recessive form); the gst c-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 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.Arg282Cys Pathogenic ★★ same residue
GDAP1 p.Arg282His Pathogenic ★★ ⚠ 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-arg282 (accessed [today's date]).

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