Is SUMF1 p.Ala177= (c.531T>A) pathogenic?

SUMF1 p.Ala177= (c.531T>A) is classified Likely benign in SUMF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). Absent from gnomAD v4.1; Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Ala177= (c.531T>A)?

SUMF1 p.Ala177= (c.531T>A) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Ala177= (c.531T>A) in the general population?

SUMF1 p.Ala177= (c.531T>A) is absent from gnomAD v4.1 (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

SUMF1 p.Ala177=

c.531T>A · rs2469868747 · VCV2749024

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.9	GERP 1.1, phastCons 1
Overall
CADD	10.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SUMF1
Protein: p.Ala177=
Coding: c.531T>A
MANE Select: NM_182760
dbSNP: rs2469868747
Type: single nucleotide variant
Location: chr3:4420135 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB
Residue 177: a UniProt-annotated variant site (in msd; loss of activity; decreases its specific enzyme activity to less than 1%; does not affect localization of the protein in the endoplasmic reticulum of msd fibroblasts; protein stability is almost comparable to wild-type)

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.Ala177Pro Pathogenic/Likely pathogenic ★★ same residue
SUMF1 p.Ala177Val 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-ala177 (accessed [today's date]).

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