Is SLMAP p.Lys583del (c.1747_1749del) pathogenic?

SLMAP p.Lys583del (c.17471749del) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). Very rare (popmax 0.00017%, nfe); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Lys583del (c.1747_1749del)?

SLMAP p.Lys583del (c.1747_1749del) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Lys583del (c.1747_1749del) in the general population?

SLMAP p.Lys583del (c.1747_1749del) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Brugada syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SLMAP p.Lys583del

c.1747_1749del · rs2475837101 · VCV2771932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.6	GERP 1.3, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,780 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,906 alleles · very rare exomes 2/1,461,586 · genomes 0/152,320 · 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: SLMAP
Protein: p.Lys583del
Coding: c.1747_1749del
MANE Select: NM_001377540
dbSNP: rs2475837101
Type: Deletion
Location: chr3:57912426 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB

Full SLMAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brugada syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brugada syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SLMAP p.Lys583Glu Uncertain significance ★★ same residue
SLMAP p.Leu146_Pro147del Uncertain significance ★★ same condition
SLMAP c.828+11del Benign ★★ same condition
SLMAP c.1501+1del Uncertain significance ★ same condition
SLMAP p.Glu245fs Uncertain significance ★ same condition
SLMAP p.Glu302fs Uncertain significance ★ same condition
SLMAP c.1300+8del Likely benign ★ same condition
SLMAP c.1360+20_1360+21del Likely benign ★ 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/slmap-p-lys583del (accessed [today's date]).

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