Is GUSB p.Ser5fs (c.12del) pathogenic?

GUSB p.Ser5fs (c.12del) is classified Likely pathogenic in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). Very rare (popmax 0.00204%, amr); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Ser5fs (c.12del)?

GUSB p.Ser5fs (c.12del) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ser5fs (c.12del) in the general population?

GUSB p.Ser5fs (c.12del) is very rare (popmax 0.00204%, amr) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Ser5fs

c.12del · VCV3594750

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00204%, amr)

Conditions

mucopolysaccharidosis type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.4	GERP -3.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00204% Admixed American · 1/49,112 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000221% 3/1,355,916 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00204%	49,112
European (non-Finnish)	0.000177%	563,641

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.Ser5fs
Coding: c.12del
MANE Select: NM_000181
Type: Deletion
Location: chr7:65982172 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB

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.Ser5Leu Uncertain significance ★ ⚠ same residue
GUSB p.Ser5Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
GUSB p.Ser5= Likely benign ★ same residue
GUSB c.1476_1476+13del Pathogenic/Likely pathogenic ★★ same condition
GUSB c.1790-5del Benign/Likely benign ★★ same condition
GUSB c.1244+2del Likely pathogenic ★ same condition
GUSB c.560_581+13del Likely pathogenic ★ same condition
GUSB p.Ala20fs 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-ser5fs (accessed [today's date]).

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