Is SGSH p.Pro288= (c.864G>A) pathogenic?

SGSH p.Pro288= (c.864G>A) is classified Likely benign in SGSH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0593%, sas); Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Pro288= (c.864G>A)?

SGSH p.Pro288= (c.864G>A) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Pro288= (c.864G>A) in the general population?

SGSH p.Pro288= (c.864G>A) is ultra-rare (popmax 0.0593%, sas) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Pro288=

c.864G>A · rs573496328 · VCV718868

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0593%, sas)

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 -4.9	GERP -2.2
Overall
CADD	6.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0593% South Asian · 54/91,078 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.00409% 66/1,613,572 alleles · ultra-rare exomes 59/1,461,252 · genomes 7/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0593%	1,687
Remaining individualsnot grpmax-eligible	0.0096%	10,416
African / African-American	0.004%	25,015
European (non-Finnish)	0.000254%	393,343

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: SGSH
Protein: p.Pro288=
Coding: c.864G>A
MANE Select: NM_000199
dbSNP: rs573496328
Type: single nucleotide variant
Location: chr17:80212156 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB
Residue 288: an α-helix; 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.Pro288Leu 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
SGSH c.745+1G>C Pathogenic/Likely pathogenic ★★ same condition
SGSH c.89-2A>G Pathogenic/Likely pathogenic ★★ same condition
SGSH c.949+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-pro288 (accessed [today's date]).

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