Is SLMAP p.Ser758Cys (c.2272A>T) pathogenic?

SLMAP p.Ser758Cys (c.2272A>T) is classified Likely benign in SLMAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0695); Rare (popmax 0.251%, nfe); Associated with Brugada syndrome.

What condition is associated with SLMAP p.Ser758Cys (c.2272A>T)?

SLMAP p.Ser758Cys (c.2272A>T) is associated with Brugada syndrome (ClinVar).

How common is SLMAP p.Ser758Cys (c.2272A>T) in the general population?

SLMAP p.Ser758Cys (c.2272A>T) is rare (popmax 0.251%, 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.Ser758Cys (c.2272A>T)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

SLMAP p.Ser758Cys

c.2272A>T · rs143689400 · VCV416638

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.251%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Brugada syndrome

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.9	GERP 0.087, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	22.1	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 S741C vs ClinVar S758C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.251% European (non-Finnish) · 2,965/1,179,922 alleles

Filtering AF 0.244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.241%

Overall 0.2% 3,231/1,613,986 alleles · rare exomes 3,041/1,461,664 · genomes 190/152,322 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.251%	398
Remaining individualsnot grpmax-eligible	0.162%	619
Admixed American	0.08%	1,250
South Asian	0.0714%	1,401
African / African-American	0.036%	2,780
Finnishnot grpmax-eligible	0.0359%	2,784
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
East Asian	0.00223%	44,806

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.Ser758Cys
Coding: c.2272A>T
MANE Select: NM_001377540
dbSNP: rs143689400
Type: single nucleotide variant
Location: chr3:57917039 (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-ser758cys (accessed [today's date]).

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