Is ARSB p.Arg95Gln (c.284G>A) pathogenic?

ARSB p.Arg95Gln (c.284G>A) is classified Pathogenic/Likely pathogenic in ARSB (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.9405); Very rare (popmax 0.00212%, amr); Associated with ARSB-related disorder.

What condition is associated with ARSB p.Arg95Gln (c.284G>A)?

ARSB p.Arg95Gln (c.284G>A) is associated with ARSB-related disorder, mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg95Gln (c.284G>A) in the general population?

ARSB p.Arg95Gln (c.284G>A) is very rare (popmax 0.00212%, amr) (gnomAD).

What do computational predictors say about ARSB p.Arg95Gln (c.284G>A)?

AlphaMissense predicts likely pathogenic (score 0.9405) — an in-silico prediction, not a clinical call.

ARSB p.Arg95Gln

c.284G>A · rs118203942 · VCV884

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARSB-related disorder

Computational evidence

Protein change
AlphaMissense	0.9405	likely pathogenic ✓ concordant with ClinVar · top 10% in ARSB
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -14.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Overall
CADD	33.0	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 0.00212% Admixed American · 1/47,132 alleles

Filtering AF 0.00026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000537% 8/1,488,434 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00212%	47,132
European (non-Finnish)	0.000626%	159,865

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.Arg95Gln
Coding: c.284G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs118203942
Type: single nucleotide variant
Location: chr5:78984965 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 95: a β-strand; a disulfide bond

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

Disease context

ARSB-related disorder

Also linked: mucopolysaccharidosis type 6

Similar variants

ARSB p.Arg95Leu Likely pathogenic ★ same residue
ARSB p.Arg95Trp Likely pathogenic ★ same residue
ARSB p.Arg95= 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

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-arg95gln (accessed [today's date]).

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