Is GUSB p.Gln187= (c.561A>G) pathogenic?

GUSB p.Gln187= (c.561A>G) is classified Benign in GUSB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). Low-frequency (popmax 2.5%, afr); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Gln187= (c.561A>G)?

GUSB p.Gln187= (c.561A>G) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Gln187= (c.561A>G) in the general population?

GUSB p.Gln187= (c.561A>G) is low-frequency (popmax 2.5%, afr) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Gln187=

c.561A>G · rs74430256 · VCV558974

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.5%, afr)

Conditions

mucopolysaccharidosis type 7

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 -0.59	GERP -3.1
Overall
CADD	1.436	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.5% African / African-American · 1,878/75,014 alleles

Filtering AF 2.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.37%

Overall 0.131% 2,107/1,613,686 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.5%	40
Remaining individualsnot grpmax-eligible	0.157%	638
Admixed American	0.138%	723
Middle Eastern	0.033%	3,030
South Asian	0.00549%	18,215
European (non-Finnish)	0.00347%	28,780

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.Gln187=
Coding: c.561A>G
MANE Select: NM_000181
dbSNP: rs74430256
Type: single nucleotide variant
Location: chr7:65979747 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 187: 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 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
GUSB p.Arg357Ter 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-gln187 (accessed [today's date]).

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