Is SUMF1 p.Pro202= (c.606G>A) pathogenic?

SUMF1 p.Pro202= (c.606G>A) is classified Conflicting classifications of pathogenicity in SUMF1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0132%, sas); Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Pro202= (c.606G>A)?

SUMF1 p.Pro202= (c.606G>A) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Pro202= (c.606G>A) in the general population?

SUMF1 p.Pro202= (c.606G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Pro202=

c.606G>A · rs141957829 · VCV345317

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Conditions

mucosulfatidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -8.4	GERP -5.5
Overall
CADD	7.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,060 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0076%

Overall 0.0129% 208/1,613,864 alleles · ultra-rare exomes 185/1,461,734 · genomes 23/152,130 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.216%	463
Remaining individualsnot grpmax-eligible	0.0256%	3,904
South Asiangrpmax	0.0132%	7,588
European (non-Finnish)	0.00958%	10,443
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00156%	64,024
African / African-American	0.00133%	74,912

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro202=
Coding: c.606G>A
MANE Select: NM_182760
dbSNP: rs141957829
Type: single nucleotide variant
Location: chr3:4418129 (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.Pro202Leu Uncertain significance ★★ ⚠ same residue
SUMF1 p.Pro202Gln Uncertain significance ★ ⚠ same residue
SUMF1 p.Pro202Arg 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

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-pro202 (accessed [today's date]).

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