Is SLMAP p.Asp481= (c.1443C>T) pathogenic?

SLMAP p.Asp481= (c.1443C>T) is classified Benign in SLMAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 51.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Brugada syndrome.

What condition is associated with SLMAP p.Asp481= (c.1443C>T)?

SLMAP p.Asp481= (c.1443C>T) is associated with Brugada syndrome (ClinVar).

How is Brugada syndrome inherited?

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

SLMAP p.Asp481=

Q: How common is SLMAP p.Asp481= (c.1443C>T) in the general population?

SLMAP p.Asp481= (c.1443C>T) is common (popmax 51.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1443C>T · rs17058639 · VCV516749

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 51.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.127	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -3, phastCons 0.51
Overall
CADD	6.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51.7% East Asian · 23,103/44,696 alleles

Filtering AF 51.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 50.9%

Overall 26.4% 422,951/1,602,862 alleles · common exomes 385,207/1,450,940 · genomes 37,744/151,922 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	51.7%	2
Admixed American	35%	3
Ashkenazi Jewishnot grpmax-eligible	34.5%	3
South Asian	34.4%	3
Middle Eastern	33.3%	3
Amishnot grpmax-eligible	31%	3
Finnishnot grpmax-eligible	29.3%	3
Remaining individualsnot grpmax-eligible	27.7%	4
European (non-Finnish)	24.6%	4
African / African-American	15.7%	6

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.Asp481=
Coding: c.1443C>T
MANE Select: NM_001377540
dbSNP: rs17058639
Type: single nucleotide variant
Location: chr3:57896874 (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-asp481 (accessed [today's date]).

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