Is GUSB p.His509= (c.1527C>T) pathogenic?

GUSB p.His509= (c.1527C>T) is classified Likely benign in GUSB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0183%, amr); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.His509= (c.1527C>T)?

GUSB p.His509= (c.1527C>T) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.His509= (c.1527C>T) in the general population?

GUSB p.His509= (c.1527C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.His509=

c.1527C>T · rs201928248 · VCV1626457

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

mucopolysaccharidosis type 7

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 · G>C here scores Δ0.55 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.1	GERP -3.7
Overall
CADD	0.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/59,988 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0126% 202/1,606,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,453
Middle Eastern	0.0164%	6,082
European (non-Finnish)	0.0153%	6,553
Remaining individualsnot grpmax-eligible	0.00961%	10,404
African / African-American	0.004%	24,971
East Asian	0.00223%	44,884

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.His509=
Coding: c.1527C>T
MANE Select: NM_000181
dbSNP: rs201928248
Type: single nucleotide variant
Location: chr7:65967857 (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.His509Gln Uncertain significance ★★ ⚠ same residue
GUSB p.His509fs Likely pathogenic ★ 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

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-his509 (accessed [today's date]).

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