Is ARSB p.Leu32del (c.91TTG[1]) pathogenic?

ARSB p.Leu32del (c.91TTG[1]) is classified Uncertain significance in ARSB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-28). Ultra-rare (popmax 0.016%, nfe); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Leu32del (c.91TTG[1])?

ARSB p.Leu32del (c.91TTG[1]) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Leu32del (c.91TTG[1]) in the general population?

ARSB p.Leu32del (c.91TTG[1]) is ultra-rare (popmax 0.016%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Leu32del

c.91TTG[1] · rs535493472 · VCV648449

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, nfe)

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 · substitutions only
Constraint at this position
Conservation	phyloP -0.008	GERP -2.7
Overall
CADD	6.904	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(CAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% European (non-Finnish) · 176/1,102,524 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0132%

Overall 0.0129% 188/1,455,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.016%	6,264
Admixed American	0.0123%	8,131
Remaining individualsnot grpmax-eligible	0.0109%	9,198
African / African-American	0.00146%	68,518

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.Leu32del
Coding: c.91TTG[1]
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs535493472
Type: Microsatellite
Location: chr5:78985153 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 32: the upar/ly6 domain; a disulfide bond

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.Leu32_Ala33insLeu Uncertain significance ★ same residue
ARSB p.Leu32= Likely benign ★ same residue
ARSB p.Tyr86del Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Leu232fs Likely pathogenic ★ same condition
ARSB c.1337-19GTTTT[3] Likely benign ★ same condition
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

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-leu32del (accessed [today's date]).

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