Is SUMF1 p.Ser359= (c.1077G>A) pathogenic?

SUMF1 p.Ser359= (c.1077G>A) is classified Benign/Likely benign in SUMF1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Rare (popmax 0.99%, afr); Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Ser359= (c.1077G>A)?

SUMF1 p.Ser359= (c.1077G>A) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Ser359= (c.1077G>A) in the general population?

SUMF1 p.Ser359= (c.1077G>A) is rare (popmax 0.99%, afr) (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Ser359=

c.1077G>A · rs140751492 · VCV459635

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.99%, afr)

Conditions

mucosulfatidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -4
Overall
CADD	4.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.99% African / African-American · 743/75,050 alleles

Filtering AF 0.931% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.907%

Overall 0.0522% 842/1,614,192 alleles · rare exomes 454/1,461,864 · genomes 388/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.99%	101
Remaining individualsnot grpmax-eligible	0.064%	1,563
Admixed American	0.0633%	1,580
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,361
European (non-Finnish)	0.00144%	69,413

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: SUMF1
Protein: p.Ser359=
Coding: c.1077G>A
MANE Select: NM_182760
dbSNP: rs140751492
Type: single nucleotide variant
Location: chr3:4362192 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB
Residue 359: the 'interaction with sulfatases' region; a UniProt-annotated variant site (in msd; almost abolished enzyme activity)

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.Ser359Ter Pathogenic/Likely pathogenic ★★ same residue
SUMF1 p.Ser359Leu Uncertain significance ★ ⚠ same residue
SUMF1 c.271-1G>C Likely pathogenic ★★ same condition
SUMF1 c.445-1G>A Pathogenic/Likely pathogenic ★★ same condition
SUMF1 c.445-2A>G Pathogenic/Likely pathogenic ★★ same condition
SUMF1 c.520-1G>C Likely pathogenic ★★ same condition
SUMF1 c.602+1G>A Pathogenic/Likely pathogenic ★★ same condition
SUMF1 c.603-1G>C 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-ser359 (accessed [today's date]).

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