Is SUMF1 p.Ala32Val (c.95C>T) pathogenic?

SUMF1 p.Ala32Val (c.95C>T) is classified Benign/Likely benign in SUMF1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1134); Rare (popmax 0.684%, sas); Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Ala32Val (c.95C>T)?

SUMF1 p.Ala32Val (c.95C>T) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Ala32Val (c.95C>T) in the general population?

SUMF1 p.Ala32Val (c.95C>T) is rare (popmax 0.684%, sas) (gnomAD).

How is Multiple sulfatase deficiency inherited?

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

What do computational predictors say about SUMF1 p.Ala32Val (c.95C>T)?

AlphaMissense predicts likely benign (score 0.1134) — an in-silico prediction, not a clinical call.

SUMF1 p.Ala32Val

c.95C>T · rs374677940 · VCV345328

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1134 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.684%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucosulfatidosis

Computational evidence

Protein change
AlphaMissense	0.1134	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.38	donor gain · deltas
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 105 kb · p 0.0001 · regional, not allelic
Overall
CADD	19.17	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.684% South Asian · 600/87,742 alleles

Filtering AF 0.639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.62%

Overall 0.0407% 646/1,587,508 alleles · rare exomes 620/1,435,196 · genomes 26/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.684%	146
Middle Eastern	0.0793%	1,260
Remaining individualsnot grpmax-eligible	0.0489%	2,046
Admixed American	0.00354%	28,217
European (non-Finnish)	0.000856%	116,808

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.Ala32Val
Coding: c.95C>T
MANE Select: NM_182760
dbSNP: rs374677940
Type: single nucleotide variant
Location: chr3:4467151 (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 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-ala32val (accessed [today's date]).

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