Is GUSB p.Ala130= (c.390C>T) pathogenic?

GUSB p.Ala130= (c.390C>T) is classified Likely benign in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-18). Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Ala130= (c.390C>T)?

GUSB p.Ala130= (c.390C>T) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ala130= (c.390C>T) in the general population?

GUSB p.Ala130= (c.390C>T) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Ala130=

c.390C>T · rs2484845325 · VCV2722977

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.63	GERP 1.5, phastCons 0.98
Overall
CADD	9.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GUSB
Protein: p.Ala130=
Coding: c.390C>T
MANE Select: NM_000181
dbSNP: rs2484845325
Type: single nucleotide variant
Location: chr7:65980230 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 130: 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.Ala130Thr 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-ala130 (accessed [today's date]).

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