Is GUSB p.Ala2= (c.6C>G) pathogenic?

GUSB p.Ala2= (c.6C>G) is classified Likely benign in GUSB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.084%, sas); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Ala2= (c.6C>G)?

GUSB p.Ala2= (c.6C>G) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ala2= (c.6C>G) in the general population?

GUSB p.Ala2= (c.6C>G) is ultra-rare (popmax 0.084%, sas) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Ala2=

c.6C>G · rs758903707 · VCV2045909

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.084%, sas)

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 -1.5	GERP -2
Overall
CADD	4.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.084% South Asian · 69/82,178 alleles

Filtering AF 0.068% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0622%

Overall 0.00628% 95/1,512,916 alleles · ultra-rare exomes 90/1,360,548 · genomes 5/152,368 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.084%	1,191
Middle Eastern	0.019%	5,252
Remaining individualsnot grpmax-eligible	0.00512%	19,528
European (non-Finnish)	0.00195%	51,399

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.Ala2=
Coding: c.6C>G
MANE Select: NM_000181
dbSNP: rs758903707
Type: single nucleotide variant
Location: chr7:65982178 (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.Ala2Val 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-ala2 (accessed [today's date]).

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