Is GUSB p.Ser5Pro (c.13T>C) pathogenic?

GUSB p.Ser5Pro (c.13T>C) is classified Conflicting classifications of pathogenicity in GUSB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0813); Rare (popmax 0.36%, eas); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Ser5Pro (c.13T>C)?

GUSB p.Ser5Pro (c.13T>C) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ser5Pro (c.13T>C) in the general population?

GUSB p.Ser5Pro (c.13T>C) is rare (popmax 0.36%, eas) (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.Ser5Pro (c.13T>C)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

GUSB p.Ser5Pro

c.13T>C · rs190496263 · VCV360557

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.36%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 7

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -3.1
Regional constraint	o/e 1.01	unconstrained · MANE · 6,069 bp · p 0.83 · regional, not allelic
Overall
CADD	0.568	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 0.36% East Asian · 137/38,040 alleles

Filtering AF 0.311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.292%

Overall 0.0119% 179/1,507,820 alleles · rare exomes 146/1,355,946 · genomes 33/151,874 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.36%	278
Remaining individualsnot grpmax-eligible	0.036%	2,776
South Asian	0.0184%	5,449
African / African-American	0.00429%	23,291
European (non-Finnish)	0.000266%	375,769

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.Ser5Pro
Coding: c.13T>C
MANE Select: NM_000181
dbSNP: rs190496263
Type: single nucleotide variant
Location: chr7:65982171 (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.Ser5Leu Uncertain significance ★ ⚠ same residue
GUSB p.Ser5= Likely benign ★ same residue
GUSB p.Ser5fs 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

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-ser5pro (accessed [today's date]).

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