Is ARSB p.Ala33Val (c.98C>T) pathogenic?

ARSB p.Ala33Val (c.98C>T) is classified Benign/Likely benign in ARSB (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1055); Low-frequency (popmax 1.34%, nfe); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Ala33Val (c.98C>T)?

ARSB p.Ala33Val (c.98C>T) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Ala33Val (c.98C>T) in the general population?

ARSB p.Ala33Val (c.98C>T) is low-frequency (popmax 1.34%, nfe) (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.Ala33Val (c.98C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

ARSB p.Ala33Val

c.98C>T · rs201168448 · VCV193036

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -1.8
Overall
CADD	4.415	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 1.34% European (non-Finnish) · 14,776/1,101,914 alleles

Filtering AF 1.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 1.22% 17,684/1,453,254 alleles · low-frequency exomes 16,196/1,301,780 · genomes 1,488/151,474 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.99%	33
European (non-Finnish)grpmax	1.34%	75
Remaining individualsnot grpmax-eligible	1.18%	84
Ashkenazi Jewishnot grpmax-eligible	0.983%	102
Admixed American	0.779%	128
Amishnot grpmax-eligible	0.439%	228
African / African-American	0.2%	499
Middle Eastern	0.127%	789
South Asian	0.0283%	3,536
East Asian	0.00287%	34,828

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala33Val
Coding: c.98C>T
MANE Select: NM_000046
dbSNP: rs201168448
Type: single nucleotide variant
Location: chr5:78985151 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 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 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
ARSB c.1213+6T>C 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-ala33val (accessed [today's date]).

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