Is SUMF1 p.Leu8= (c.22C>T) pathogenic?

SUMF1 p.Leu8= (c.22C>T) is classified Likely benign in SUMF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-27). Rare (popmax 0.142%, amr); Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Leu8= (c.22C>T)?

SUMF1 p.Leu8= (c.22C>T) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Leu8= (c.22C>T) in the general population?

SUMF1 p.Leu8= (c.22C>T) is rare (popmax 0.142%, amr) (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Leu8=

c.22C>T · rs769257869 · VCV1589125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.142%, amr)

Conditions

mucosulfatidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 2	GERP -1.5, phastCons 0.013
Overall
CADD	10.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% Admixed American · 85/59,772 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.00571% 92/1,610,948 alleles · rare exomes 41/1,458,738 · genomes 51/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.142%	703
African / African-American	0.00134%	74,872
European (non-Finnish)	0.000509%	196,503

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.Leu8=
Coding: c.22C>T
MANE Select: NM_182760
dbSNP: rs769257869
Type: single nucleotide variant
Location: chr3:4467224 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB

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.Leu8Val Uncertain significance ★ ⚠ same residue
SUMF1 p.Leu8Pro Likely benign ★ 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-leu8 (accessed [today's date]).

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