Is GUSB p.Ser539= (c.1617C>T) pathogenic?

GUSB p.Ser539= (c.1617C>T) is classified Pathogenic/Likely pathogenic in GUSB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-05). Very rare (popmax 0.00966%, nfe); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Ser539= (c.1617C>T)?

GUSB p.Ser539= (c.1617C>T) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ser539= (c.1617C>T) in the general population?

GUSB p.Ser539= (c.1617C>T) is very rare (popmax 0.00966%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Ser539=

c.1617C>T · rs377519272 · VCV901

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00966%, nfe)

Conditions

mucopolysaccharidosis type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.85	donor gain · deltas
Pangolin	Δ0.75	gain · loss 0.31 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.9	GERP -0.34, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00966% European (non-Finnish) · 114/1,179,856 alleles

Filtering AF 0.00818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00725% 117/1,613,440 alleles · very rare exomes 111/1,461,242 · genomes 6/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00966%	10,350
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,466
South Asian	0.0011%	91,082

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: GUSB
Protein: p.Ser539=
Coding: c.1617C>T
MANE Select: NM_000181
dbSNP: rs377519272
Type: single nucleotide variant
Location: chr7:65967767 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 539: a β-strand

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

Disease context

mucopolysaccharidosis type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 7 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Antenatal, Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

GUSB p.Ser539Arg Uncertain significance ★★ ⚠ same residue
GUSB c.1244+1G>A Pathogenic ★★ same condition
GUSB c.581+1G>A Pathogenic/Likely pathogenic ★★ same condition
GUSB c.724+1G>T Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Ala619Val Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg110Ter Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg167Ter Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg216Trp 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/gusb-p-ser539 (accessed [today's date]).

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