Is ARSB p.Val143fs (c.427del) pathogenic?

ARSB p.Val143fs (c.427del) is classified Pathogenic in ARSB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00254%, nfe); Associated with ARSB-related disorder.

What condition is associated with ARSB p.Val143fs (c.427del)?

ARSB p.Val143fs (c.427del) is associated with ARSB-related disorder, mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Val143fs (c.427del) in the general population?

ARSB p.Val143fs (c.427del) is very rare (popmax 0.00254%, nfe) (gnomAD).

ARSB p.Val143fs

c.427del · rs766914147 · VCV559782

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Conditions

ARSB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,180,022 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00229% 37/1,613,928 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00781%	12,802
European (non-Finnish)grpmax	0.00254%	39,334
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00134%	74,852

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.Val143fs
Coding: c.427del
MANE Select: NM_000046
dbSNP: rs766914147
Type: Deletion
Location: chr5:78969078 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 143: a β-strand

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.Val143= Likely benign ★ same residue
ARSB p.Ala39fs Pathogenic ★★ same condition
ARSB p.Gly38fs Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Gly40fs Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Leu354fs Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Pro248fs Pathogenic ★★ same condition
ARSB p.Ser37fs Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Thr526fs 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-val143fs (accessed [today's date]).

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