Is NAGLU p.Ser141= (c.423T>C) pathogenic?

NAGLU p.Ser141= (c.423T>C) is classified Benign/Likely benign in NAGLU (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with mucopolysaccharidosis type 3B.

What condition is associated with NAGLU p.Ser141= (c.423T>C)?

NAGLU p.Ser141= (c.423T>C) is associated with mucopolysaccharidosis type 3B, Charcot-Marie-Tooth disease axonal type 2V (ClinVar).

How is Mucopolysaccharidosis type 3 inherited?

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

NAGLU p.Ser141=

Q: How common is NAGLU p.Ser141= (c.423T>C) in the general population?

NAGLU p.Ser141= (c.423T>C) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.423T>C · rs659497 · VCV92694

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

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 1.7	GERP -2.5, phastCons 1
Overall
CADD	12.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,878/44,878 alleles

Filtering AF 99.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 99%

Overall 99.3% 1,603,057/1,614,250 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Amishnot grpmax-eligible	100%	1
African / African-American	99.9%	1
South Asian	99.8%	1
Admixed American	99.6%	1
Finnishnot grpmax-eligible	99.5%	1
Remaining individualsnot grpmax-eligible	99.2%	1
European (non-Finnish)	99.2%	1
Middle Eastern	99.2%	1
Ashkenazi Jewishnot grpmax-eligible	98.9%	1

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: NAGLU
Protein: p.Ser141=
Coding: c.423T>C
MANE Select: NM_000263
dbSNP: rs659497
Type: single nucleotide variant
Location: chr17:42537437 (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

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.Ser141Thr Benign ★★ ⚠ same residue
NAGLU p.Ser141Phe 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

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-ser141 (accessed [today's date]).

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