Is ARSB p.Pro511= (c.1533C>T) pathogenic?

ARSB p.Pro511= (c.1533C>T) is classified Conflicting classifications of pathogenicity in ARSB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-25). Ultra-rare (popmax 0.056%, afr); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Pro511= (c.1533C>T)?

ARSB p.Pro511= (c.1533C>T) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Pro511= (c.1533C>T) in the general population?

ARSB p.Pro511= (c.1533C>T) is ultra-rare (popmax 0.056%, afr) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Pro511=

c.1533C>T · rs528157833 · VCV354303

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, 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 -11	GERP -3.7
Overall
CADD	0.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% African / African-American · 42/75,036 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00582% 94/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.056%	1,787
Middle Eastern	0.0165%	6,060
East Asian	0.00668%	14,961
Remaining individualsnot grpmax-eligible	0.0064%	15,628
South Asian	0.00549%	18,218
European (non-Finnish)	0.00331%	30,257

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.Pro511=
Coding: c.1533C>T
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs528157833
Type: single nucleotide variant
Location: chr5:78780466 (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-pro511 (accessed [today's date]).

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