Is ARSB p.Ile220Val (c.658A>G) pathogenic?

ARSB p.Ile220Val (c.658A>G) is classified Conflicting classifications of pathogenicity in ARSB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0695); Rare (popmax 0.241%, eas); Associated with Inborn genetic diseases.

What condition is associated with ARSB p.Ile220Val (c.658A>G)?

ARSB p.Ile220Val (c.658A>G) is associated with Inborn genetic diseases, mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Ile220Val (c.658A>G) in the general population?

ARSB p.Ile220Val (c.658A>G) is rare (popmax 0.241%, eas) (gnomAD).

What do computational predictors say about ARSB p.Ile220Val (c.658A>G)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

ARSB p.Ile220Val

c.658A>G · rs202130413 · VCV1108226

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.241%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -5.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.035	GERP -1.6
Overall
CADD	7.487	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.241% East Asian · 108/44,874 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.00954% 154/1,614,092 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.241%	415
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.00769%	13,011
European (non-Finnish)	0.00254%	39,331

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.Ile220Val
Coding: c.658A>G
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs202130413
Type: single nucleotide variant
Location: chr5:78964448 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

Full ARSB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 6

Similar variants

ARSB p.Ile220fs Likely pathogenic ★ 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-ile220val (accessed [today's date]).

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