Is ARSB p.Asp480= (c.1440C>T) pathogenic?

ARSB p.Asp480= (c.1440C>T) is classified Likely benign in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Ultra-rare (popmax 0.0318%, sas); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Asp480= (c.1440C>T)?

ARSB p.Asp480= (c.1440C>T) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Asp480= (c.1440C>T) in the general population?

ARSB p.Asp480= (c.1440C>T) is ultra-rare (popmax 0.0318%, sas) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Asp480=

c.1440C>T · rs556943300 · VCV1080099

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, sas)

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 4.6	GERP 0.89, phastCons 1
Overall
CADD	8.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0318% South Asian · 29/91,074 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00198% 32/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0318%	3,140
Remaining individualsnot grpmax-eligible	0.0048%	20,836

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.Asp480=
Coding: c.1440C>T
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs556943300
Type: single nucleotide variant
Location: chr5:78780559 (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 p.Asp480Tyr Uncertain significance ⚠ same residue
ARSB p.Asp480fs Conflicting classifications of pathogenicity ★ same residue
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

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-asp480 (accessed [today's date]).

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