Is SLMAP p.Ser99= (c.297C>T) pathogenic?

SLMAP p.Ser99= (c.297C>T) is classified Benign/Likely benign in SLMAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Rare (popmax 0.191%, amr); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Ser99= (c.297C>T)?

SLMAP p.Ser99= (c.297C>T) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Ser99= (c.297C>T) in the general population?

SLMAP p.Ser99= (c.297C>T) is rare (popmax 0.191%, 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.Ser99=

c.297C>T · rs190769315 · VCV697272

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.191%, amr)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.2	GERP -4.4
Overall
CADD	7.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.191% Admixed American · 111/57,980 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.152%

Overall 0.0113% 180/1,594,134 alleles · rare exomes 112/1,442,212 · genomes 68/151,922 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.191%	522
Remaining individualsnot grpmax-eligible	0.0293%	3,415
Middle Eastern	0.0167%	6,002
African / African-American	0.00405%	24,683
European (non-Finnish)	0.00376%	26,579
South Asian	0.00228%	43,898
East Asian	0.00227%	43,966

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.Ser99=
Coding: c.297C>T
MANE Select: NM_001377540
dbSNP: rs190769315
Type: single nucleotide variant
Location: chr3:57831481 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB
Residue 99: the 'necessary for targeting to centrosomes' 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 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-ser99 (accessed [today's date]).

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