Is SGSH p.Phe225= (c.675C>T) pathogenic?

SGSH p.Phe225= (c.675C>T) is classified Benign in SGSH (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.9%, afr); Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Phe225= (c.675C>T)?

SGSH p.Phe225= (c.675C>T) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Phe225= (c.675C>T) in the general population?

SGSH p.Phe225= (c.675C>T) is low-frequency (popmax 1.9%, afr) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Phe225=

c.675C>T · rs34520362 · VCV528318

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.9%, afr)

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.67	GERP -0.95
Overall
CADD	11.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.9% African / African-American · 1,422/75,034 alleles

Filtering AF 1.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.78%

Overall 0.105% 1,682/1,607,950 alleles · low-frequency exomes 863/1,455,608 · genomes 819/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.9%	53
Middle Eastern	0.182%	550
Remaining individualsnot grpmax-eligible	0.138%	725
Admixed American	0.121%	827
European (non-Finnish)	0.00729%	13,712
South Asian	0.00554%	18,056

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: SGSH
Protein: p.Phe225=
Coding: c.675C>T
MANE Select: NM_000199
dbSNP: rs34520362
Type: single nucleotide variant
Location: chr17:80213874 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB

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.Phe225Leu Conflicting classifications of pathogenicity ★ ⚠ 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-phe225 (accessed [today's date]).

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