Is ARSB p.Arg345Gln (c.1034G>A) pathogenic?

ARSB p.Arg345Gln (c.1034G>A) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-19). AlphaMissense: likely benign (0.075); Very rare (popmax 0.00195%, nfe); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Arg345Gln (c.1034G>A)?

ARSB p.Arg345Gln (c.1034G>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg345Gln (c.1034G>A) in the general population?

ARSB p.Arg345Gln (c.1034G>A) is very rare (popmax 0.00195%, 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.Arg345Gln (c.1034G>A)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

ARSB p.Arg345Gln

c.1034G>A · rs148067062 · VCV1003876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -3.19	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 0.69, phastCons 1
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,180,012 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00167% 27/1,613,918 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,305
Admixed American	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00134%	74,888
South Asian	0.0011%	91,072

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.Arg345Gln
Coding: c.1034G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs148067062
Type: single nucleotide variant
Location: chr5:78885692 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 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 p.Arg345Trp 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
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-arg345gln (accessed [today's date]).

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