Is SLMAP p.Thr688= (c.2064C>T) pathogenic?

SLMAP p.Thr688= (c.2064C>T) is classified Benign/Likely benign in SLMAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Low-frequency (popmax 1%, afr); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Thr688= (c.2064C>T)?

SLMAP p.Thr688= (c.2064C>T) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Thr688= (c.2064C>T) in the general population?

SLMAP p.Thr688= (c.2064C>T) is low-frequency (popmax 1%, afr) (gnomAD).

How is Brugada syndrome inherited?

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

SLMAP p.Thr688=

c.2064C>T · rs146313438 · VCV416633

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1%, afr)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -5.1
Overall
CADD	0.763	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1% African / African-American · 751/74,738 alleles

Filtering AF 0.945% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.921%

Overall 0.0811% 1,296/1,598,420 alleles · low-frequency exomes 838/1,446,316 · genomes 458/152,104 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1%	100
South Asian	0.358%	279
Middle Eastern	0.2%	500
Remaining individualsnot grpmax-eligible	0.183%	546
Admixed American	0.0652%	1,534
European (non-Finnish)	0.00522%	19,162
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,288

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.Thr688=
Coding: c.2064C>T
MANE Select: NM_001377540
dbSNP: rs146313438
Type: single nucleotide variant
Location: chr3:57913201 (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-thr688 (accessed [today's date]).

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