Is ARSB p.Glu482= (c.1446A>G) pathogenic?

ARSB p.Glu482= (c.1446A>G) is classified Benign in ARSB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.9%, afr); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Glu482= (c.1446A>G)?

ARSB p.Glu482= (c.1446A>G) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Glu482= (c.1446A>G) in the general population?

ARSB p.Glu482= (c.1446A>G) is low-frequency (popmax 3.9%, afr) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Glu482=

c.1446A>G · rs35714924 · VCV354306

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.9%, afr)

Conditions

mucopolysaccharidosis type 6

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 1.2	GERP -0.4, phastCons 1
Overall
CADD	8.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.9% African / African-American · 2,924/75,020 alleles

Filtering AF 3.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.73%

Overall 0.212% 3,429/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.9%	26
Admixed American	0.357%	280
Middle Eastern	0.313%	319
Remaining individualsnot grpmax-eligible	0.262%	381
South Asian	0.0121%	8,280
European (non-Finnish)	0.00822%	12,165

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: ARSB
Protein: p.Glu482=
Coding: c.1446A>G
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs35714924
Type: single nucleotide variant
Location: chr5:78780553 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

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

Disease context

mucopolysaccharidosis type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 6 (Orphanet):

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

Similar variants

ARSB c.1142+1G>A Pathogenic ★★ same condition
ARSB c.1142+1G>T Pathogenic ★★ same condition
ARSB c.1142+2T>A Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1142+2T>C Pathogenic ★★ same condition
ARSB c.1143-1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1143-1G>C Pathogenic ★★ same condition
ARSB c.1143-8T>G Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1213+6T>C 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/arsb-p-glu482 (accessed [today's date]).

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