Is SGSH p.Pro299= (c.897G>A) pathogenic?

SGSH p.Pro299= (c.897G>A) is classified Likely benign in SGSH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-27). Very rare (popmax 0.00891%, eas); Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Pro299= (c.897G>A)?

SGSH p.Pro299= (c.897G>A) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Pro299= (c.897G>A) in the general population?

SGSH p.Pro299= (c.897G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Pro299=

c.897G>A · rs147061152 · VCV2142560

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 -11	GERP -2.2
Overall
CADD	0.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00459% 74/1,613,462 alleles · very rare exomes 71/1,461,288 · genomes 3/152,174 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
European (non-Finnish)	0.00559%	17,879
Admixed American	0.00167%	59,988
Finnishnot grpmax-eligible	0.00158%	63,456
African / African-American	0.00133%	74,934
South Asian	0.0011%	91,086

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.Pro299=
Coding: c.897G>A
MANE Select: NM_000199
dbSNP: rs147061152
Type: single nucleotide variant
Location: chr17:80212123 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB

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.Pro299Leu 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-pro299 (accessed [today's date]).

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