Is GUSB p.Phe149= (c.447C>T) pathogenic?

GUSB p.Phe149= (c.447C>T) is classified Likely benign in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Ultra-rare (popmax 0.0142%, nfe); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Phe149= (c.447C>T)?

GUSB p.Phe149= (c.447C>T) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Phe149= (c.447C>T) in the general population?

GUSB p.Phe149= (c.447C>T) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Phe149=

c.447C>T · rs148364905 · VCV1156249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

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>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.6	GERP -2.8
Overall
CADD	0.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0142% European (non-Finnish) · 167/1,179,772 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0113% 183/1,612,858 alleles · ultra-rare exomes 167/1,460,714 · genomes 16/152,144 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0142%	7,064
Finnishnot grpmax-eligible	0.0126%	7,937
East Asian	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.0032%	31,213
African / African-American	0.00267%	37,450
South Asian	0.0022%	45,525

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.Phe149=
Coding: c.447C>T
MANE Select: NM_000181
dbSNP: rs148364905
Type: single nucleotide variant
Location: chr7:65979861 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 149: 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 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
GUSB p.Arg357Ter 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-phe149 (accessed [today's date]).

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