Is SGSH p.Pro329= (c.987G>A) pathogenic?

SGSH p.Pro329= (c.987G>A) is classified Likely benign in SGSH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). Ultra-rare (popmax 0.0164%, mid); Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Pro329= (c.987G>A)?

SGSH p.Pro329= (c.987G>A) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Pro329= (c.987G>A) in the general population?

SGSH p.Pro329= (c.987G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Pro329=

c.987G>A · rs752176531 · VCV1094042

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.11	GERP -2.6, phastCons 0.21
Overall
CADD	8.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.001% 16/1,599,786 alleles · ultra-rare exomes 11/1,447,636 · genomes 5/152,150 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00534%	18,726
Admixed American	0.00333%	29,998
Remaining individualsnot grpmax-eligible	0.00321%	31,191
South Asian	0.0011%	91,084
European (non-Finnish)	0.000509%	196,640

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.Pro329=
Coding: c.987G>A
MANE Select: NM_000199
dbSNP: rs752176531
Type: single nucleotide variant
Location: chr17:80210974 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB
Residue 329: 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 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
SGSH p.Ala63Asp 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-pro329 (accessed [today's date]).

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