SLC18A3 p.Ala433=
c.1299G>C · rs769077516 · VCV2171450
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00415%, nfe)
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 -0.76 | GERP -4.1 |
| Overall | ||
| CADD | 6.692 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00415%
European (non-Finnish) · 49/1,179,982 alleles
Filtering AF
0.00318%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00286%
Overall
0.00322%
52/1,613,580 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00415% | 24,081 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| African / African-American | 0.00267% | 37,466 |
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
- SLC18A3
- Protein
- p.Ala433=
- Coding
- c.1299G>C
- MANE Select
- NM_003055
- dbSNP
- rs769077516
- Type
- single nucleotide variant
- Location
- chr10:49612039 (GRCh38)
- Gene constraint
- LOEUF 1.213 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.88 · 11 PDB
- Residue 433
- an α-helix
Similar variants
- SLC18A3 p.Ala14Asp Uncertain significance ★★ ⚠ same type
- SLC18A3 p.Arg30Trp Uncertain significance ★★ ⚠ same type
- SLC18A3 p.Pro375= Benign/Likely benign ★★ same type
- SLC18A3 p.Trp315Ter Likely pathogenic ★ same type
- SLC18A3 p.Ala14Val Conflicting classifications of pathogenicity ★ ⚠ same type
- SLC18A3 p.Arg412Ser Uncertain significance ★ ⚠ same type
- SLC18A3 p.Asp152Glu Uncertain significance ★ ⚠ same type
- SLC18A3 p.Asp202Tyr 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/slc18a3-p-ala433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown