Is SUMF1 p.Asp213Val (c.638A>T) pathogenic?

SUMF1 p.Asp213Val (c.638A>T) is classified Uncertain significance in SUMF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely pathogenic (0.9856); Very rare (popmax 0.0011%, sas); Associated with mucosulfatidosis.

What condition is associated with SUMF1 p.Asp213Val (c.638A>T)?

SUMF1 p.Asp213Val (c.638A>T) is associated with mucosulfatidosis (ClinVar).

How common is SUMF1 p.Asp213Val (c.638A>T) in the general population?

SUMF1 p.Asp213Val (c.638A>T) is very rare (popmax 0.0011%, 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.Asp213Val (c.638A>T)?

AlphaMissense predicts likely pathogenic (score 0.9856) — an in-silico prediction, not a clinical call.

SUMF1 p.Asp213Val

c.638A>T · rs781215980 · VCV1427391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucosulfatidosis

Computational evidence

Protein change
AlphaMissense	0.9856	likely pathogenic · top 6% in SUMF1
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -16.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 105 kb · p 0.0001 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,614,082 alleles · very rare exomes 1/1,461,804 · genomes 0/152,278 · joint denominator

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.Asp213Val
Coding: c.638A>T
MANE Select: NM_182760
dbSNP: rs781215980
Type: single nucleotide variant
Location: chr3:4418097 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB
Residue 213: an α-helix

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-asp213val (accessed [today's date]).

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