Is GDAP1 p.Arg120Gly (c.358C>G) pathogenic?

GDAP1 p.Arg120Gly (c.358C>G) is classified Uncertain significance in GDAP1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2016-01-06). AlphaMissense: likely pathogenic (0.9755); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease.

What condition is associated with GDAP1 p.Arg120Gly (c.358C>G)?

GDAP1 p.Arg120Gly (c.358C>G) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease axonal type 2K (ClinVar).

How common is GDAP1 p.Arg120Gly (c.358C>G) in the general population?

GDAP1 p.Arg120Gly (c.358C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GDAP1 p.Arg120Gly (c.358C>G)?

AlphaMissense predicts likely pathogenic (score 0.9755) — an in-silico prediction, not a clinical call.

GDAP1 p.Arg120Gly

c.358C>G · rs104894078 · VCV637112

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.9755	likely pathogenic
REVEL	0.752	pathogenic-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GDAP1
Protein: p.Arg120Gly
Coding: c.358C>G
MANE Select: NM_018972
dbSNP: rs104894078
Type: single nucleotide variant
Location: chr8:74360184 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 120: a UniProt-annotated variant site (in cmt2k; dominant form); a UniProt-annotated variant site (in cmt4a; no effect on mitochondrial localization but impairment in the ability to induce mitochondrial fragmentation); a UniProt-annotated variant site (in cmt2k; dominant form; no effect on mitochondrial localization); 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 axonal type 2K

Similar variants

GDAP1 p.Arg120Trp Pathogenic ★★ ⚠ same residue
GDAP1 p.Arg120Gln Uncertain significance ⚠ same residue
GDAP1 p.Arg120Leu Likely pathogenic ★ ⚠ same residue
GDAP1 p.Arg120= Likely benign ★ 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.Arg125Ter 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-arg120gly (accessed [today's date]).

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