Is ARSB p.Pro248= (c.744T>A) pathogenic?

ARSB p.Pro248= (c.744T>A) is classified Likely benign in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-10). Very rare (popmax 0.00133%, afr); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Pro248= (c.744T>A)?

ARSB p.Pro248= (c.744T>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Pro248= (c.744T>A) in the general population?

ARSB p.Pro248= (c.744T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ARSB p.Pro248=

c.744T>A · rs764599728 · VCV1966391

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.3
Overall
CADD	0.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,930 alleles

Overall 0.000657% 1/152,232 alleles · very rare

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.Pro248=
Coding: c.744T>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs764599728
Type: single nucleotide variant
Location: chr5:78955449 (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.Pro248fs Pathogenic ★★ 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-pro248 (accessed [today's date]).

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