Is ARSB p.Glu243= (c.729G>A) pathogenic?

ARSB p.Glu243= (c.729G>A) is classified Likely benign in ARSB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Ultra-rare (popmax 0.0582%, sas); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Glu243= (c.729G>A)?

ARSB p.Glu243= (c.729G>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Glu243= (c.729G>A) in the general population?

ARSB p.Glu243= (c.729G>A) is ultra-rare (popmax 0.0582%, sas) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Glu243=

c.729G>A · rs144029271 · VCV743048

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, 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 -0.27	GERP -4.3, phastCons 0.1
Overall
CADD	11.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0582% South Asian · 53/91,074 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00483% 78/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0582%	1,718
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.016%	6,251
African / African-American	0.00267%	37,523
European (non-Finnish)	0.000847%	118,002

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.Glu243=
Coding: c.729G>A
MANE Select: NM_000046
dbSNP: rs144029271
Type: single nucleotide variant
Location: chr5:78955464 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 243: a disulfide bond; a β-strand

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.Glu243_Pro244delinsAspSer 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
ARSB c.1143-1G>C Pathogenic ★★ same condition
ARSB c.1143-8T>G 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-glu243 (accessed [today's date]).

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