Is ARSB p.Val358Met (c.1072G>A) pathogenic?

ARSB p.Val358Met (c.1072G>A) is classified Benign in ARSB (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.24); Common (popmax 43.9%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Val358Met (c.1072G>A)?

ARSB p.Val358Met (c.1072G>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

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.Val358Met (c.1072G>A)?

AlphaMissense predicts likely benign (score 0.24) — an in-silico prediction, not a clinical call.

ARSB p.Val358Met

Q: How common is ARSB p.Val358Met (c.1072G>A) in the general population?

ARSB p.Val358Met (c.1072G>A) is common (popmax 43.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1072G>A · rs1065757 · VCV92350

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.24 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 43.9%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.24	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -9.72	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 3.3	GERP 0.68, phastCons 1
Overall
CADD	24.1	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 43.9% European (non-Finnish) · 518,366/1,179,914 alleles

Filtering AF 43.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.8%

Overall 41.3% 665,917/1,613,786 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	58.1%	2
Amishnot grpmax-eligible	48.5%	2
European (non-Finnish)grpmax	43.9%	2
Admixed American	42.1%	2
Remaining individualsnot grpmax-eligible	39.5%	3
East Asian	37.5%	3
Ashkenazi Jewishnot grpmax-eligible	34%	3
Middle Eastern	33.1%	3
South Asian	25.7%	4
African / African-American	10.3%	10

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val358Met
Coding: c.1072G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs1065757
Type: single nucleotide variant
Location: chr5:78885654 (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.Val358Leu Uncertain significance ★ ⚠ same residue
ARSB p.Val358= 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

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-val358met (accessed [today's date]).

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