Is ARSB p.Arg152Gln (c.455G>A) pathogenic?

ARSB p.Arg152Gln (c.455G>A) is classified Likely pathogenic in ARSB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0718); Ultra-rare (popmax 0.033%, mid); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Arg152Gln (c.455G>A)?

ARSB p.Arg152Gln (c.455G>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg152Gln (c.455G>A) in the general population?

ARSB p.Arg152Gln (c.455G>A) is ultra-rare (popmax 0.033%, mid) (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.Arg152Gln (c.455G>A)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

ARSB p.Arg152Gln

c.455G>A · rs776814144 · VCV800876

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign ⚠ discordant with ClinVar
REVEL	0.361	indeterminate
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.54, phastCons 1
Overall
CADD	21.2	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00233% 34/1,461,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Admixed American	0.0133%	7,502
South Asian	0.0121%	8,280
East Asian	0.00668%	14,961
African / African-American	0.00267%	37,518
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000593%	168,576

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.Arg152Gln
Coding: c.455G>A
MANE Select: NM_000046
dbSNP: rs776814144
Type: single nucleotide variant
Location: chr5:78969050 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 152: a disulfide bond; 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.Arg152Trp 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-arg152gln (accessed [today's date]).

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