Is SLMAP p.Asp478Asn (c.1432G>A) pathogenic?

SLMAP p.Asp478Asn (c.1432G>A) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). AlphaMissense: ambiguous (0.4074); Very rare (popmax 0.00222%, sas); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Asp478Asn (c.1432G>A)?

SLMAP p.Asp478Asn (c.1432G>A) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Asp478Asn (c.1432G>A) in the general population?

SLMAP p.Asp478Asn (c.1432G>A) is very rare (popmax 0.00222%, sas) (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.Asp478Asn (c.1432G>A)?

AlphaMissense predicts ambiguous (score 0.4074) — an in-silico prediction, not a clinical call.

SLMAP p.Asp478Asn

c.1432G>A · rs1016820088 · VCV532097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.4074	ambiguous
REVEL	0.719	pathogenic-leaning
SaProt	LLR -6.18	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, 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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D461N vs ClinVar D478N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00222% South Asian · 2/90,020 alleles

Filtering AF 0.000369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000373% 6/1,607,870 alleles · very rare exomes 6/1,455,688 · genomes 0/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00222%	45,010
African / African-American	0.00134%	74,754
European (non-Finnish)	0.000255%	392,280

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.Asp478Asn
Coding: c.1432G>A
MANE Select: NM_001377540
dbSNP: rs1016820088
Type: single nucleotide variant
Location: chr3:57896582 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB
Residue 461 UniProt numbering: the 'disordered' region

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.Asp478Tyr 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-asp478asn (accessed [today's date]).

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