Is SLMAP p.Ala445= (c.1335G>A) pathogenic?

SLMAP p.Ala445= (c.1335G>A) is classified Likely benign in SLMAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0164%, mid); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Ala445= (c.1335G>A)?

SLMAP p.Ala445= (c.1335G>A) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Ala445= (c.1335G>A) in the general population?

SLMAP p.Ala445= (c.1335G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Brugada syndrome inherited?

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

SLMAP p.Ala445=

c.1335G>A · rs148417939 · VCV699685

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.244	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -4, phastCons 0.99
Overall
CADD	7.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00868% 140/1,613,686 alleles · ultra-rare exomes 134/1,461,604 · genomes 6/152,082 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.011%	9,075
Remaining individualsnot grpmax-eligible	0.0048%	20,823
African / African-American	0.00401%	24,957
East Asian	0.00223%	44,876
South Asian	0.0022%	45,532

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.Ala445=
Coding: c.1335G>A
MANE Select: NM_001377540
dbSNP: rs148417939
Type: single nucleotide variant
Location: chr3:57890075 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB
Residue 445: the 'disordered' region

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.Ala445Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala445 (accessed [today's date]).

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