Is SLMAP p.Arg706Trp (c.2116C>T) pathogenic?

SLMAP p.Arg706Trp (c.2116C>T) is classified Conflicting classifications of pathogenicity in SLMAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-16). AlphaMissense: likely benign (0.1004); Ultra-rare (popmax 0.0437%, amr); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Arg706Trp (c.2116C>T)?

SLMAP p.Arg706Trp (c.2116C>T) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Arg706Trp (c.2116C>T) in the general population?

SLMAP p.Arg706Trp (c.2116C>T) is ultra-rare (popmax 0.0437%, amr) (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.Arg706Trp (c.2116C>T)?

AlphaMissense predicts likely benign (score 0.1004) — an in-silico prediction, not a clinical call.

SLMAP p.Arg706Trp

c.2116C>T · rs188700768 · VCV696847

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0437%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.1004	likely benign
REVEL	0.329	indeterminate
SaProt	LLR -10.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R689W vs ClinVar R706W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0437% Admixed American · 26/59,436 alleles

Filtering AF 0.0306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00973% 152/1,562,226 alleles · ultra-rare exomes 140/1,410,030 · genomes 12/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0437%	2,286
Middle Eastern	0.017%	5,886
European (non-Finnish)	0.00965%	10,368
African / African-American	0.00808%	12,372
East Asian	0.00678%	14,755
Finnishnot grpmax-eligible	0.0048%	20,825
Remaining individualsnot grpmax-eligible	0.00332%	30,137
South Asian	0.00117%	85,490

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.Arg706Trp
Coding: c.2116C>T
MANE Select: NM_001377540
dbSNP: rs188700768
Type: single nucleotide variant
Location: chr3:57913253 (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.Arg706Gln 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-arg706trp (accessed [today's date]).

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