Is ARSB p.Arg152Trp (c.454C>T) pathogenic?

ARSB p.Arg152Trp (c.454C>T) is classified Pathogenic in ARSB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.1866); Very rare (popmax 0.00568%, nfe); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Arg152Trp (c.454C>T)?

ARSB p.Arg152Trp (c.454C>T) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg152Trp (c.454C>T) in the general population?

ARSB p.Arg152Trp (c.454C>T) is very rare (popmax 0.00568%, 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.Arg152Trp (c.454C>T)?

AlphaMissense predicts likely benign (score 0.1866) — an in-silico prediction, not a clinical call.

ARSB p.Arg152Trp

c.454C>T · rs991104525 · VCV496789

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.1866	likely benign ⚠ discordant with ClinVar
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -12.82	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Overall
CADD	27.5	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 0.00568% European (non-Finnish) · 67/1,180,030 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.0044% 71/1,614,012 alleles · very rare exomes 60/1,461,878 · genomes 11/152,134 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,612
Finnishnot grpmax-eligible	0.00312%	32,010
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,080

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.Arg152Trp
Coding: c.454C>T
MANE Select: NM_000046
dbSNP: rs991104525
Type: single nucleotide variant
Location: chr5:78969051 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 152: a UniProt-annotated variant site (in mps6; intermediate form)

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.Arg152Gln Likely pathogenic ★★ ⚠ same residue
ARSB p.Arg152= Benign/Likely benign ★★ same residue
ARSB p.Arg152Leu 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-arg152trp (accessed [today's date]).

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