Is SGSH p.Pro293= (c.879C>G) pathogenic?

SGSH p.Pro293= (c.879C>G) is classified Likely benign in SGSH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Pro293= (c.879C>G)?

SGSH p.Pro293= (c.879C>G) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Pro293= (c.879C>G) in the general population?

SGSH p.Pro293= (c.879C>G) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Pro293=

c.879C>G · rs2144716366 · VCV1571706

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

mucopolysaccharidosis type 3A

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 1.1	GERP -1.4, phastCons 0.57
Overall
CADD	2.874	PHRED · no single calibrated threshold — expert panels disagree

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: SGSH
Protein: p.Pro293=
Coding: c.879C>G
MANE Select: NM_000199
dbSNP: rs2144716366
Type: single nucleotide variant
Location: chr17:80212141 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB
Residue 293: a UniProt-annotated variant site (in mps3a; does not yield active enzyme; the reduction in 62 kda precursor and 56 kda mature forms suggests an increased degradation of the mutant enzyme); a UniProt-annotated variant site (in mps3a)

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.Pro293Ser Pathogenic/Likely pathogenic ★★ same residue
SGSH p.Pro293Arg Uncertain significance ★ ⚠ same residue
SGSH p.Pro293Leu Uncertain significance ★ ⚠ same residue
SGSH p.Pro293Thr Uncertain significance ★ ⚠ 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-pro293 (accessed [today's date]).

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