Is SGSH p.Phe60= (c.180T>C) pathogenic?

SGSH p.Phe60= (c.180T>C) is classified Likely benign in SGSH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Phe60= (c.180T>C)?

SGSH p.Phe60= (c.180T>C) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Phe60= (c.180T>C) in the general population?

SGSH p.Phe60= (c.180T>C) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Phe60=

c.180T>C · rs2144781750 · VCV2769961

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 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.204	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP -1.2, phastCons 1
Overall
CADD	9.521	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: SGSH
Protein: p.Phe60=
Coding: c.180T>C
MANE Select: NM_000199
dbSNP: rs2144781750
Type: single nucleotide variant
Location: chr17:80217101 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB
Residue 60: a β-strand

Full SGSH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucopolysaccharidosis type 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Brazil)

Similar variants

SGSH p.Phe60_Leu78del Pathogenic ★ same residue
SGSH c.250-2A>G Pathogenic/Likely pathogenic ★★ same condition
SGSH c.356-1G>A Pathogenic/Likely pathogenic ★★ same condition
SGSH c.356-2A>G Pathogenic/Likely pathogenic ★★ same condition
SGSH c.506+1G>A Pathogenic/Likely pathogenic ★★ same condition
SGSH c.745+1G>C Pathogenic/Likely pathogenic ★★ same condition
SGSH c.89-2A>G Pathogenic/Likely pathogenic ★★ same condition
SGSH c.949+1G>A 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/sgsh-p-phe60 (accessed [today's date]).

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