Is ARSB p.Arg388Thr (c.1163G>C) pathogenic?

ARSB p.Arg388Thr (c.1163G>C) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-01). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Arg388Thr (c.1163G>C)?

ARSB p.Arg388Thr (c.1163G>C) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg388Thr (c.1163G>C) in the general population?

ARSB p.Arg388Thr (c.1163G>C) is absent from gnomAD v4.1 (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.Arg388Thr (c.1163G>C)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

ARSB p.Arg388Thr

c.1163G>C · rs1554074134 · VCV559684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic · top 1% in ARSB
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -15.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARSB
Protein: p.Arg388Thr
Coding: c.1163G>C
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs1554074134
Type: single nucleotide variant
Location: chr5:78839406 (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.Arg388fs Likely 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-arg388thr (accessed [today's date]).

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