Is SUMF1 p.Ala173= (c.519A>G) pathogenic?

SUMF1 p.Ala173= (c.519A>G) is classified Conflicting classifications of pathogenicity in SUMF1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0379%, nfe); Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Ala173= (c.519A>G)?

SUMF1 p.Ala173= (c.519A>G) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Ala173= (c.519A>G) in the general population?

SUMF1 p.Ala173= (c.519A>G) is ultra-rare (popmax 0.0379%, nfe) (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Ala173=

c.519A>G · rs146050361 · VCV345320

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, nfe)

Conditions

mucosulfatidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.24	GERP 0.34, phastCons 1
Overall
CADD	12.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% European (non-Finnish) · 447/1,179,990 alleles

Filtering AF 0.0349% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0338%

Overall 0.044% 710/1,614,174 alleles · ultra-rare exomes 648/1,461,814 · genomes 62/152,360 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.309%	323
Remaining individualsnot grpmax-eligible	0.0464%	2,155
European (non-Finnish)grpmax	0.0379%	2,640
Middle Eastern	0.033%	3,031
South Asian	0.0329%	3,036
African / African-American	0.00533%	18,767

Finnish 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.Ala173=
Coding: c.519A>G
MANE Select: NM_182760
dbSNP: rs146050361
Type: single nucleotide variant
Location: chr3:4449266 (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.Ala173Ser 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
SUMF1 c.840+1G>A 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-ala173 (accessed [today's date]).

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