Is SLMAP p.Arg748Gln (c.2243G>A) pathogenic?

SLMAP p.Arg748Gln (c.2243G>A) is classified Uncertain significance in SLMAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-16). AlphaMissense: likely benign (0.0648); Ultra-rare (popmax 0.0446%, eas); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Arg748Gln (c.2243G>A)?

SLMAP p.Arg748Gln (c.2243G>A) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Arg748Gln (c.2243G>A) in the general population?

SLMAP p.Arg748Gln (c.2243G>A) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

How is Brugada syndrome inherited?

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

What do computational predictors say about SLMAP p.Arg748Gln (c.2243G>A)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

SLMAP p.Arg748Gln

c.2243G>A · rs141277984 · VCV1432218

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R731Q vs ClinVar R748Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% East Asian · 20/44,824 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.0039% 63/1,613,738 alleles · ultra-rare exomes 60/1,461,680 · genomes 3/152,058 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,241
Admixed American	0.00667%	14,994
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.0028%	35,755
African / African-American	0.00267%	37,446
South Asian	0.0022%	45,536

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.Arg748Gln
Coding: c.2243G>A
MANE Select: NM_001377540
dbSNP: rs141277984
Type: single nucleotide variant
Location: chr3:57917010 (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.Arg748Trp 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-arg748gln (accessed [today's date]).

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