Is SGSH p.Phe136fs (c.407_408del) pathogenic?

SGSH p.Phe136fs (c.407408del) is classified Likely pathogenic in SGSH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). Very rare (popmax 0.00167%, amr); Associated with mucopolysaccharidosis type 3A.

What condition is associated with SGSH p.Phe136fs (c.407_408del)?

SGSH p.Phe136fs (c.407_408del) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is SGSH p.Phe136fs (c.407_408del) in the general population?

SGSH p.Phe136fs (c.407_408del) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

SGSH p.Phe136fs

c.407_408del · VCV4061354

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,032 alleles

Overall 0.000124% 2/1,613,270 alleles · very rare exomes 2/1,460,938 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,032
European (non-Finnish)	8.47e-05%	1,179,999

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.Phe136fs
Coding: c.407_408del
MANE Select: NM_000199
Type: Deletion
Location: chr17:80214713 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.64 · 2 PDB
Residue 136: 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.Phe136Ile Uncertain significance ★ ⚠ same residue
SGSH p.Phe136= Likely benign ★ same residue
SGSH p.Ala231fs Pathogenic/Likely pathogenic ★★ same condition
SGSH p.Ala232fs Pathogenic/Likely pathogenic ★★ same condition
SGSH p.Arg385fs Pathogenic/Likely pathogenic ★★ same condition
SGSH p.Asn151fs Likely pathogenic ★★ same condition
SGSH p.Gln449fs Pathogenic/Likely pathogenic ★★ same condition
SGSH p.His476fs 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-phe136fs (accessed [today's date]).

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