Is ARSB p.Ser65Phe (c.194C>T) pathogenic?

ARSB p.Ser65Phe (c.194C>T) is classified Conflicting classifications of pathogenicity in ARSB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-10). AlphaMissense: likely pathogenic (0.6498); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Ser65Phe (c.194C>T)?

ARSB p.Ser65Phe (c.194C>T) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Ser65Phe (c.194C>T) in the general population?

ARSB p.Ser65Phe (c.194C>T) 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.Ser65Phe (c.194C>T)?

AlphaMissense predicts likely pathogenic (score 0.6498) — an in-silico prediction, not a clinical call.

ARSB p.Ser65Phe

c.194C>T · rs1233331806 · VCV559735

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6498 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,541,968)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.6498	likely pathogenic
REVEL	0.955	strongly pathogenic-leaning
SaProt	LLR -15.97	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 9.2	GERP 0.63, phastCons 1
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,541,968). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARSB
Protein: p.Ser65Phe
Coding: c.194C>T
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs1233331806
Type: single nucleotide variant
Location: chr5:78985055 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 65: the upar/ly6 domain; a disulfide bond

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 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
ARSB c.1213+6T>C 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-ser65phe (accessed [today's date]).

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