Is GUSB p.Asn84Ser (c.251A>G) pathogenic?

GUSB p.Asn84Ser (c.251A>G) is classified Uncertain significance in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-21). AlphaMissense: likely benign (0.222); Very rare (popmax 0.00133%, afr); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Asn84Ser (c.251A>G)?

GUSB p.Asn84Ser (c.251A>G) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Asn84Ser (c.251A>G) in the general population?

GUSB p.Asn84Ser (c.251A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

What do computational predictors say about GUSB p.Asn84Ser (c.251A>G)?

AlphaMissense predicts likely benign (score 0.222) — an in-silico prediction, not a clinical call.

GUSB p.Asn84Ser

c.251A>G · rs765042077 · VCV2041338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucopolysaccharidosis type 7

Computational evidence

Protein change
AlphaMissense	0.222	likely benign
REVEL	0.548	indeterminate
SaProt	LLR -10.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.24, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 6,069 bp · p 0.83 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,788 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.000339%	294,984

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.Asn84Ser
Coding: c.251A>G
MANE Select: NM_000181
dbSNP: rs765042077
Type: single nucleotide variant
Location: chr7:65980369 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 84: a turn

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.Asn84= Likely benign ★ 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-asn84ser (accessed [today's date]).

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