Is SLMAP p.Leu165= (c.495A>G) pathogenic?

SLMAP p.Leu165= (c.495A>G) is classified Benign/Likely benign in SLMAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Rare (popmax 0.263%, nfe); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Leu165= (c.495A>G)?

SLMAP p.Leu165= (c.495A>G) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Leu165= (c.495A>G) in the general population?

SLMAP p.Leu165= (c.495A>G) is rare (popmax 0.263%, 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.Leu165=

c.495A>G · rs149758819 · VCV240723

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.263%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.48, phastCons 1
Overall
CADD	7.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.263% European (non-Finnish) · 3,005/1,143,286 alleles

Filtering AF 0.255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.255% 4,011/1,573,820 alleles · rare exomes 3,647/1,421,482 · genomes 364/152,338 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.922%	108
Ashkenazi Jewishnot grpmax-eligible	0.473%	211
European (non-Finnish)grpmax	0.263%	380
Remaining individualsnot grpmax-eligible	0.231%	434
Admixed American	0.128%	779
African / African-American	0.0539%	1,857
Middle Eastern	0.05%	1,999
South Asian	0.0166%	6,013
East Asian	0.00224%	44,702

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu165=
Coding: c.495A>G
MANE Select: NM_001377540
dbSNP: rs149758819
Type: single nucleotide variant
Location: chr3:57849792 (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-leu165 (accessed [today's date]).

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