Is ARSB p.Val342Met (c.1024G>A) pathogenic?

ARSB p.Val342Met (c.1024G>A) is classified Uncertain significance in ARSB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-01). AlphaMissense: likely benign (0.089); Very rare (popmax 0.00892%, eas); Associated with Inborn genetic diseases.

What condition is associated with ARSB p.Val342Met (c.1024G>A)?

ARSB p.Val342Met (c.1024G>A) is associated with Inborn genetic diseases, mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Val342Met (c.1024G>A) in the general population?

ARSB p.Val342Met (c.1024G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about ARSB p.Val342Met (c.1024G>A)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

ARSB p.Val342Met

c.1024G>A · rs749593643 · VCV2080128

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -7.98	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 0.43	GERP -0.25, phastCons 0.032
Overall
CADD	18.24	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 0.00892% East Asian · 4/44,868 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00308% 45/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,217
European (non-Finnish)	0.00331%	30,257
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,034

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.Val342Met
Coding: c.1024G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs749593643
Type: single nucleotide variant
Location: chr5:78885702 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 6

Similar variants

ARSB p.Val342= 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
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-val342met (accessed [today's date]).

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