Is SLMAP p.Ala640= (c.1920G>A) pathogenic?

SLMAP p.Ala640= (c.1920G>A) is classified Likely benign in SLMAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-16). Very rare (popmax 0.00891%, eas); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Ala640= (c.1920G>A)?

SLMAP p.Ala640= (c.1920G>A) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Ala640= (c.1920G>A) in the general population?

SLMAP p.Ala640= (c.1920G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Brugada syndrome inherited?

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

SLMAP p.Ala640=

c.1920G>A · rs149493923 · VCV1780705

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.109	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -4.5
Overall
CADD	2.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00105% 17/1,614,136 alleles · very rare exomes 16/1,461,798 · genomes 1/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
African / African-American	0.00266%	37,536
South Asian	0.0022%	45,543
European (non-Finnish)	0.000763%	131,111

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.Ala640=
Coding: c.1920G>A
MANE Select: NM_001377540
dbSNP: rs149493923
Type: single nucleotide variant
Location: chr3:57912601 (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 p.Ala640Val Uncertain significance ★ ⚠ 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-ala640 (accessed [today's date]).

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