Is SLMAP p.Gly309Arg (c.925G>A) pathogenic?

SLMAP p.Gly309Arg (c.925G>A) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely pathogenic (0.6627); Absent from gnomAD v4.1; Associated with Brugada syndrome.

What condition is associated with SLMAP p.Gly309Arg (c.925G>A)?

SLMAP p.Gly309Arg (c.925G>A) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Gly309Arg (c.925G>A) in the general population?

SLMAP p.Gly309Arg (c.925G>A) is absent from gnomAD v4.1 (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.Gly309Arg (c.925G>A)?

AlphaMissense predicts likely pathogenic (score 0.6627) — an in-silico prediction, not a clinical call.

SLMAP p.Gly309Arg

c.925G>A · VCV3721411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.6627	likely pathogenic
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLMAP
Protein: p.Gly309Arg
Coding: c.925G>A
MANE Select: NM_001377540
Type: single nucleotide variant
Location: chr3:57862045 (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 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
SLMAP p.Arg138Cys 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-gly309arg (accessed [today's date]).

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