Is NAGLU p.Pro111fs (c.329dup) pathogenic?

NAGLU p.Pro111fs (c.329dup) is classified Pathogenic in NAGLU (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease axonal type 2V.

What condition is associated with NAGLU p.Pro111fs (c.329dup)?

NAGLU p.Pro111fs (c.329dup) is associated with Charcot-Marie-Tooth disease axonal type 2V, mucopolysaccharidosis type 3B (ClinVar).

How common is NAGLU p.Pro111fs (c.329dup) in the general population?

NAGLU p.Pro111fs (c.329dup) is absent from gnomAD (gnomAD).

NAGLU p.Pro111fs

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.329dup · rs2510650554 · VCV2011393

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.68	GERP 1.3, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NAGLU
Protein: p.Pro111fs
Coding: c.329dup
MANE Select: NM_000263
dbSNP: rs2510650554
Type: Duplication
Location: chr17:42536600 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 1 PDB

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.Pro111Leu Uncertain significance ★ ⚠ same residue
NAGLU p.His487fs Pathogenic/Likely pathogenic ★★ same condition
NAGLU p.Pro215fs Pathogenic/Likely pathogenic ★★ same condition
NAGLU p.Thr392fs Pathogenic/Likely pathogenic ★★ same condition
NAGLU p.Tyr483fs Pathogenic ★★ same condition
NAGLU p.Val12fs Pathogenic/Likely pathogenic ★★ same condition
NAGLU p.Ala364fs Pathogenic ★ same condition
NAGLU p.Gln569fs 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-pro111fs (accessed [today's date]).

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