Is SUMF1 p.Pro226fs (c.675dup) pathogenic?

SUMF1 p.Pro226fs (c.675dup) is classified Pathogenic in SUMF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-08). No gnomAD frequency available for this variant; Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Pro226fs (c.675dup)?

SUMF1 p.Pro226fs (c.675dup) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Pro226fs (c.675dup) in the general population?

SUMF1 p.Pro226fs (c.675dup) is no gnomAD frequency available for this variant (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Pro226fs

c.675dup · rs2469858380 · VCV2029578

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

mucosulfatidosis

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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SUMF1
Protein: p.Pro226fs
Coding: c.675dup
MANE Select: NM_182760
dbSNP: rs2469858380
Type: Duplication
Location: chr3:4418059 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB
Residue 226: an α-helix

Full SUMF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucosulfatidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple sulfatase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Antenatal, Childhood, Infancy, Neonatal

Similar variants

SUMF1 p.Pro226= Likely benign ★ same residue
SUMF1 p.Thr120fs Pathogenic/Likely pathogenic ★★ same condition
SUMF1 p.Trp231fs Pathogenic ★★ same condition
SUMF1 p.Ala114fs Pathogenic ★ same condition
SUMF1 p.Ala3fs Likely pathogenic ★ same condition
SUMF1 p.Arg12fs Pathogenic ★ same condition
SUMF1 p.Asn212fs Pathogenic ★ same condition
SUMF1 p.Leu6fs 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/sumf1-p-pro226fs (accessed [today's date]).

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