SLC8A1 p.Lys336=
c.1008G>A · rs1576422493 · VCV744426
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.02 | GERP -4.1, phastCons 0.82 |
| Overall | ||
| CADD | 2.908 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000136%
Overall
0.000186%
3/1,613,916 alleles · ultra-rare
exomes 3/1,461,688 · genomes 0/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| South Asian | 0.0022% | 45,544 |
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
- SLC8A1
- Protein
- p.Lys336=
- Coding
- c.1008G>A
- MANE Select
- NM_021097
- dbSNP
- rs1576422493
- Type
- single nucleotide variant
- Location
- chr2:40429273 (GRCh38)
- Gene constraint
- LOEUF 0.363 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.64 · 5 PDB
Similar variants
- SLC8A1 p.Lys336Asn Uncertain significance ★ ⚠ same residue
- SLC8A1 p.Arg929= Benign ★★ same type
- SLC8A1 p.Gly905= Benign ★★ same type
- SLC8A1 p.Ala307Val Uncertain significance ★ ⚠ same type
- SLC8A1 p.Ala322Val Uncertain significance ★ ⚠ same type
- SLC8A1 p.Ala349Gly Uncertain significance ★ ⚠ same type
- SLC8A1 p.Ala451Ser Uncertain significance ★ ⚠ same type
- SLC8A1 p.Ala504Gly Uncertain significance ★ ⚠ same type
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/slc8a1-p-lys336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown