Is SLMAP p.Arg615Pro (c.1844G>C) pathogenic?

SLMAP p.Arg615Pro (c.1844G>C) is classified Uncertain significance in SLMAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.949); Very rare (popmax 0.000424%, nfe); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Arg615Pro (c.1844G>C)?

SLMAP p.Arg615Pro (c.1844G>C) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Arg615Pro (c.1844G>C) in the general population?

SLMAP p.Arg615Pro (c.1844G>C) is very rare (popmax 0.000424%, nfe) (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.Arg615Pro (c.1844G>C)?

AlphaMissense predicts likely pathogenic (score 0.949) — an in-silico prediction, not a clinical call.

SLMAP p.Arg615Pro

c.1844G>C · rs781418237 · VCV2448009

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.949	likely pathogenic
REVEL	0.377	indeterminate
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 R598P vs ClinVar R615P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,018 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,150 alleles · very rare exomes 5/1,461,846 · genomes 0/152,304 · joint denominator

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.Arg615Pro
Coding: c.1844G>C
MANE Select: NM_001377540
dbSNP: rs781418237
Type: single nucleotide variant
Location: chr3:57912525 (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.Arg615Gln Uncertain significance ★★ ⚠ same residue
SLMAP p.Arg615Trp 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

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-arg615pro (accessed [today's date]).

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