Is ARSB p.Thr100= (c.300T>C) pathogenic?

ARSB p.Thr100= (c.300T>C) is classified Likely benign in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). Very rare (popmax 0.000365%, nfe); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Thr100= (c.300T>C)?

ARSB p.Thr100= (c.300T>C) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Thr100= (c.300T>C) in the general population?

ARSB p.Thr100= (c.300T>C) is very rare (popmax 0.000365%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Thr100=

c.300T>C · rs1753094740 · VCV1139416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000365%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -3.2, phastCons 0.98
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000365% European (non-Finnish) · 4/1,095,656 alleles

Filtering AF 8.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.8e-05%

Overall 0.000309% 4/1,293,002 alleles · very rare

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.Thr100=
Coding: c.300T>C
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs1753094740
Type: single nucleotide variant
Location: chr5:78984949 (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.Thr100Pro Uncertain significance ⚠ same residue
ARSB p.Thr100Ala Uncertain significance ★ ⚠ same residue
SLURP1 p.Asn100Ser Uncertain significance ★ ⚠ 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

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-thr100 (accessed [today's date]).

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