Is ARSB p.Val80= (c.240G>A) pathogenic?

ARSB p.Val80= (c.240G>A) is classified Likely benign in ARSB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-03). Ultra-rare (popmax 0.0299%, afr); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Val80= (c.240G>A)?

ARSB p.Val80= (c.240G>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Val80= (c.240G>A) in the general population?

ARSB p.Val80= (c.240G>A) is ultra-rare (popmax 0.0299%, afr) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

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

ARSB p.Val80=

c.240G>A · rs368338486 · VCV1125934

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0299%, 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 0.64	GERP -3, phastCons 0.68
Overall
CADD	13.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0299% African / African-American · 21/70,118 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0169%

Overall 0.0024% 37/1,538,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0299%	3,339
Remaining individualsnot grpmax-eligible	0.0204%	4,904
East Asian	0.00807%	12,391
European (non-Finnish)	8.73e-05%	1,145,696

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.Val80=
Coding: c.240G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs368338486
Type: single nucleotide variant
Location: chr5:78985009 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 80: 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.Val80fs Pathogenic ★ same residue
SLURP1 p.Thr80= Likely benign ★ 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

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-val80 (accessed [today's date]).

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