Is SLMAP p.Gln664Arg (c.1991A>G) pathogenic?

SLMAP p.Gln664Arg (c.1991A>G) is classified Likely benign in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0786); Rare (popmax 0.151%, nfe); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Gln664Arg (c.1991A>G)?

SLMAP p.Gln664Arg (c.1991A>G) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Gln664Arg (c.1991A>G) in the general population?

SLMAP p.Gln664Arg (c.1991A>G) is rare (popmax 0.151%, 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.Gln664Arg (c.1991A>G)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

SLMAP p.Gln664Arg

c.1991A>G · rs35029175 · VCV463277

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	24.4	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 Q647R vs ClinVar Q664R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% European (non-Finnish) · 1,775/1,178,764 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.142%

Overall 0.113% 1,824/1,612,582 alleles · rare exomes 1,729/1,460,216 · genomes 95/152,366 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.151%	664
Remaining individualsnot grpmax-eligible	0.0496%	2,015
African / African-American	0.0147%	6,821
Admixed American	0.01%	9,999
South Asian	0.0011%	91,080

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.Gln664Arg
Coding: c.1991A>G
MANE Select: NM_001377540
dbSNP: rs35029175
Type: single nucleotide variant
Location: chr3:57912672 (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.Gln664His Uncertain significance ★★ ⚠ same residue
SLMAP p.Gln664= Likely benign ★★ 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-gln664arg (accessed [today's date]).

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