Is NAGLU p.Pro283= (c.849G>A) pathogenic?

NAGLU p.Pro283= (c.849G>A) is classified Uncertain significance in NAGLU (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). Very rare (popmax 0.00223%, eas); Associated with mucopolysaccharidosis type 3B.

What condition is associated with NAGLU p.Pro283= (c.849G>A)?

NAGLU p.Pro283= (c.849G>A) is associated with mucopolysaccharidosis type 3B, Charcot-Marie-Tooth disease axonal type 2V (ClinVar).

How common is NAGLU p.Pro283= (c.849G>A) in the general population?

NAGLU p.Pro283= (c.849G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

NAGLU p.Pro283=

c.849G>A · rs201374620 · VCV2139346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

mucopolysaccharidosis type 3B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.91	acceptor gain · deltas
Pangolin	Δ0.75	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -7.7	GERP -4.8
Overall
CADD	19.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000867% 14/1,614,164 alleles · very rare exomes 10/1,461,886 · genomes 4/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,084
European (non-Finnish)	0.000932%	107,276

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.Pro283=
Coding: c.849G>A
MANE Select: NM_000263
dbSNP: rs201374620
Type: single nucleotide variant
Location: chr17:42541034 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 1 PDB
Residue 283: 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.Pro283Leu 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-pro283 (accessed [today's date]).

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