Is SLMAP p.Leu693= (c.2079A>G) pathogenic?

SLMAP p.Leu693= (c.2079A>G) is classified Likely benign in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-04). Very rare (popmax 0.00334%, amr); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Leu693= (c.2079A>G)?

SLMAP p.Leu693= (c.2079A>G) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Leu693= (c.2079A>G) in the general population?

SLMAP p.Leu693= (c.2079A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

How is Brugada syndrome inherited?

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

SLMAP p.Leu693=

c.2079A>G · rs1239780849 · VCV2719774

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.13	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.061	GERP -0.83, phastCons 0.032
Overall
CADD	7.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,868 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.0005% 8/1,600,720 alleles · very rare exomes 8/1,448,404 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,934
East Asian	0.00224%	44,640
Remaining individualsnot grpmax-eligible	0.00162%	61,830
European (non-Finnish)	0.000342%	292,649

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.Leu693=
Coding: c.2079A>G
MANE Select: NM_001377540
dbSNP: rs1239780849
Type: single nucleotide variant
Location: chr3:57913216 (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 c.*38C>T Uncertain significance ★★ ⚠ same condition
SLMAP c.*55G>A Uncertain significance ★★ ⚠ same condition
SLMAP c.*70G>A Uncertain significance ★★ ⚠ same condition
SLMAP p.Ala365Asp Uncertain significance ★★ ⚠ same condition
SLMAP p.Ala506Ser Uncertain significance ★★ ⚠ same condition
SLMAP p.Ala597Val Uncertain significance ★★ ⚠ same condition
SLMAP p.Arg136Gln Uncertain significance ★★ ⚠ same condition
SLMAP p.Arg138Cys Uncertain significance ★★ ⚠ 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-leu693 (accessed [today's date]).

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