Is NAGLU p.Asp489= (c.1467C>T) pathogenic?

NAGLU p.Asp489= (c.1467C>T) is classified Conflicting classifications of pathogenicity in NAGLU (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0262%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NAGLU p.Asp489= (c.1467C>T)?

NAGLU p.Asp489= (c.1467C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 3B, Charcot-Marie-Tooth disease axonal type 2V (ClinVar).

How common is NAGLU p.Asp489= (c.1467C>T) in the general population?

NAGLU p.Asp489= (c.1467C>T) is ultra-rare (popmax 0.0262%, nfe) (gnomAD).

NAGLU p.Asp489=

c.1467C>T · rs115550028 · VCV720198

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, nfe)

Conditions

Inborn genetic diseases

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 -12	GERP -4.8
Overall
CADD	0.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0262% European (non-Finnish) · 308/1,175,444 alleles

Filtering AF 0.0238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.0206% 330/1,600,274 alleles · ultra-rare exomes 304/1,447,886 · genomes 26/152,388 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0262%	3,816
Remaining individualsnot grpmax-eligible	0.0161%	6,201
Admixed American	0.0154%	6,508
African / African-American	0.00267%	37,427
East Asian	0.00226%	44,316

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.Asp489=
Coding: c.1467C>T
MANE Select: NM_000263
dbSNP: rs115550028
Type: single nucleotide variant
Location: chr17:42543473 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 1 PDB
Residue 489: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 3B Charcot-Marie-Tooth disease axonal type 2V

Similar variants

NAGLU p.Asp489fs Likely pathogenic 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-asp489 (accessed [today's date]).

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