SLC8A1 p.Asp680=
c.2040C>T · rs148845964 · VCV734795
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.072%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.6 | GERP -3.4 |
| Overall | ||
| CADD | 0.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.072%
African / African-American · 54/74,962 alleles
Filtering AF
0.0566%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0511%
Overall
0.00471%
76/1,613,692 alleles · ultra-rare
exomes 45/1,461,500 · genomes 31/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.072% | 1,388 |
| Admixed American | 0.0117% | 8,572 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| East Asian | 0.00446% | 22,425 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000763% | 131,093 |
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.Asp680=
- Coding
- c.2040C>T
- MANE Select
- NM_021097
- dbSNP
- rs148845964
- Type
- single nucleotide variant
- Location
- chr2:40164983 (GRCh38)
- Gene constraint
- LOEUF 0.363 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.64 · 5 PDB
Similar variants
- 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
- SLC8A1 p.Ala512Thr 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-asp680 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown