Is SUMF1 p.Thr372= (c.1116T>C) pathogenic?

SUMF1 p.Thr372= (c.1116T>C) is classified Benign in SUMF1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 86.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Thr372= (c.1116T>C)?

SUMF1 p.Thr372= (c.1116T>C) is associated with mucosulfatidosis (ClinVar).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Thr372=

Q: How common is SUMF1 p.Thr372= (c.1116T>C) in the general population?

SUMF1 p.Thr372= (c.1116T>C) is common (popmax 86.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1116T>C · rs2633852 · VCV96559

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 86.5%, afr) — too common for a highly-penetrant pathogenic allele

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 0.65	GERP -1.7
Overall
CADD	2.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 86.5% African / African-American · 64,926/75,032 alleles

Filtering AF 86% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.7%

Overall 58.7% 946,407/1,613,514 alleles · common exomes 845,195/1,461,346 · genomes 101,212/152,168 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	86.5%	1
East Asian	77.1%	1
South Asian	73.6%	1
Admixed American	72.1%	1
Middle Eastern	63.7%	2
Remaining individualsnot grpmax-eligible	60.6%	2
Ashkenazi Jewishnot grpmax-eligible	60.4%	2
Amishnot grpmax-eligible	60.2%	2
Finnishnot grpmax-eligible	57.6%	2
European (non-Finnish)	54.2%	2

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.Thr372=
Coding: c.1116T>C
MANE Select: NM_182760
dbSNP: rs2633852
Type: single nucleotide variant
Location: chr3:4362153 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB
Residue 372: a UniProt-annotated variant site (in msd; almost abolished enzyme activity); 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 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
SUMF1 c.840+1G>A Likely pathogenic ★★ same condition
SUMF1 c.954+1G>T 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/sumf1-p-thr372 (accessed [today's date]).

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