Is NAGLU p.Ser522= (c.1566C>A) pathogenic?

NAGLU p.Ser522= (c.1566C>A) is classified Likely benign in NAGLU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-26). Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 3B.

What condition is associated with NAGLU p.Ser522= (c.1566C>A)?

NAGLU p.Ser522= (c.1566C>A) is associated with mucopolysaccharidosis type 3B, Charcot-Marie-Tooth disease axonal type 2V (ClinVar).

How common is NAGLU p.Ser522= (c.1566C>A) in the general population?

NAGLU p.Ser522= (c.1566C>A) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

NAGLU p.Ser522=

c.1566C>A · rs2510659832 · VCV2121937

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

mucopolysaccharidosis type 3B

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 0.24	GERP 0.29, phastCons 0.98
Overall
CADD	4.343	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.Ser522=
Coding: c.1566C>A
MANE Select: NM_000263
dbSNP: rs2510659832
Type: single nucleotide variant
Location: chr17:42543572 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 1 PDB
Residue 522: a UniProt-annotated variant site (in mps3b)

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

Disease context

mucopolysaccharidosis type 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2V

For Mucopolysaccharidosis type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Brazil)

Similar variants

NAGLU p.Ser522Phe 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-ser522 (accessed [today's date]).

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