Is ARSB p.Thr100Pro (c.298A>C) pathogenic?

ARSB p.Thr100Pro (c.298A>C) is classified Uncertain significance in ARSB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely pathogenic (0.8576); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Thr100Pro (c.298A>C)?

ARSB p.Thr100Pro (c.298A>C) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Thr100Pro (c.298A>C) in the general population?

ARSB p.Thr100Pro (c.298A>C) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

What do computational predictors say about ARSB p.Thr100Pro (c.298A>C)?

AlphaMissense predicts likely pathogenic (score 0.8576) — an in-silico prediction, not a clinical call.

ARSB p.Thr100Pro

c.298A>C · VCV4061139

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8576 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,448,138)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.8576	likely pathogenic
REVEL	0.82	moderately pathogenic-leaning
SaProt	LLR -17.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.4, phastCons 1
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,448,138). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARSB
Protein: p.Thr100Pro
Coding: c.298A>C
MANE Select: NM_020427 · reported on NM_000046
Type: single nucleotide variant
Location: chr5:78984951 (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.Thr100= Likely benign ★ 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-thr100pro (accessed [today's date]).

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