Is SGSH p.Arg74= (c.222C>A) pathogenic?

SGSH p.Arg74= (c.222C>A) is classified Likely benign in SGSH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-02). No allele count reported in gnomAD v4.1 (AN 1,589,772); Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Arg74= (c.222C>A)?

SGSH p.Arg74= (c.222C>A) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Arg74= (c.222C>A) in the general population?

SGSH p.Arg74= (c.222C>A) is no allele count reported in gnomAD v4.1 (AN 1,589,772) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Arg74=

c.222C>A · rs768056322 · VCV2833994

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,772)

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.063	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -2
Overall
CADD	0.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,772). 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: SGSH
Protein: p.Arg74=
Coding: c.222C>A
MANE Select: NM_000199
dbSNP: rs768056322
Type: single nucleotide variant
Location: chr17:80217059 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB
Residue 74: a UniProt-annotated variant site (in mps3a; intermediate/severe; the mutant is enzymatically inactive; rapid degradation rather than decrease in synthesis is responsible for the low steady state level of the mutant protein in cells; the majority of newly synthesized protein probably occurs in the endoplasmic reticulum); a UniProt-annotated variant site (in mps3a); an α-helix

Full SGSH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucopolysaccharidosis type 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Brazil)

Similar variants

SGSH p.Arg74Cys Pathogenic/Likely pathogenic ★★ same residue
SGSH p.Arg74His Pathogenic/Likely pathogenic ★★ same residue
SGSH p.Arg74Ser Likely pathogenic ★ same residue
SGSH p.Arg74Leu Pathogenic same residue
SGSH c.250-2A>G Pathogenic/Likely pathogenic ★★ same condition
SGSH c.356-1G>A Pathogenic/Likely pathogenic ★★ same condition
SGSH c.356-2A>G Pathogenic/Likely pathogenic ★★ same condition
SGSH c.506+1G>A 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/sgsh-p-arg74 (accessed [today's date]).

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