Is SLMAP p.Ile102Val (c.304A>G) pathogenic?

SLMAP p.Ile102Val (c.304A>G) is classified Uncertain significance in SLMAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0932); Ultra-rare (popmax 0.0173%, amr); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Ile102Val (c.304A>G)?

SLMAP p.Ile102Val (c.304A>G) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Ile102Val (c.304A>G) in the general population?

SLMAP p.Ile102Val (c.304A>G) is ultra-rare (popmax 0.0173%, 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.Ile102Val (c.304A>G)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

SLMAP p.Ile102Val

c.304A>G · rs756212703 · VCV1512636

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 74 kb · p 4.7e-09 · regional, not allelic
Overall
CADD	23.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% Admixed American · 10/57,846 alleles

Filtering AF 0.00931% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00704%

Overall 0.00107% 17/1,594,292 alleles · ultra-rare exomes 15/1,442,124 · genomes 2/152,168 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0173%	5,785
Remaining individualsnot grpmax-eligible	0.00163%	61,480
European (non-Finnish)	0.000513%	194,950

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.Ile102Val
Coding: c.304A>G
MANE Select: NM_001377540
dbSNP: rs756212703
Type: single nucleotide variant
Location: chr3:57831488 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB
Residue 102: the 'necessary for targeting to centrosomes' region; a β-strand

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-ile102val (accessed [today's date]).

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