Is NAGLU p.Arg593= (c.1779G>A) pathogenic?

NAGLU p.Arg593= (c.1779G>A) is classified Likely benign in NAGLU (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease axonal type 2V.

What condition is associated with NAGLU p.Arg593= (c.1779G>A)?

NAGLU p.Arg593= (c.1779G>A) is associated with Charcot-Marie-Tooth disease axonal type 2V, mucopolysaccharidosis type 3B (ClinVar).

How common is NAGLU p.Arg593= (c.1779G>A) in the general population?

NAGLU p.Arg593= (c.1779G>A) is absent from gnomAD v4.1 (gnomAD).

NAGLU p.Arg593=

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2V inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1779G>A · rs2143113596 · VCV1566913

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease axonal type 2V

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 3.3	GERP -2.1, phastCons 1
Overall
CADD	1.522	PHRED · no single calibrated threshold — expert panels disagree

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: NAGLU
Protein: p.Arg593=
Coding: c.1779G>A
MANE Select: NM_000263
dbSNP: rs2143113596
Type: single nucleotide variant
Location: chr17:42543785 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 1 PDB
Residue 593: an α-helix; a UniProt-annotated variant site (in mps3b)

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

Disease context

Charcot-Marie-Tooth disease axonal type 2V — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 3B

For Autosomal dominant Charcot-Marie-Tooth disease type 2V (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Elderly

Similar variants

NAGLU p.Arg593Lys Uncertain significance ★ ⚠ same residue
NAGLU c.1021+1G>A Likely pathogenic ★★ same condition
NAGLU c.1022-2A>G Pathogenic/Likely pathogenic ★★ same condition
NAGLU c.383+1G>T Pathogenic/Likely pathogenic ★★ same condition
NAGLU c.384-1G>A Pathogenic ★★ same condition
NAGLU c.531+1G>A Pathogenic ★★ same condition
NAGLU c.531+1G>C Pathogenic ★★ same condition
NAGLU c.678+1G>A 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/naglu-p-arg593 (accessed [today's date]).

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