SLC18A2 p.Phe377=
c.1131T>C · rs750330569 · VCV725482
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0756%, amr)
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 0.92 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 14.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0756%
Admixed American · 45/59,554 alleles
Filtering AF
0.058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0518%
Overall
0.00403%
63/1,563,952 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0756% | 1,323 |
| Middle Eastern | 0.0174% | 5,736 |
| Ashkenazi Jewishnot grpmax-eligible | 0.014% | 7,141 |
| Remaining individualsnot grpmax-eligible | 0.01% | 9,961 |
| African / African-American | 0.00134% | 74,400 |
| European (non-Finnish) | 0.000526% | 190,229 |
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
- SLC18A2
- Protein
- p.Phe377=
- Coding
- c.1131T>C
- MANE Select
- NM_003054
- dbSNP
- rs750330569
- Type
- single nucleotide variant
- Location
- chr10:117267681 (GRCh38)
- Gene constraint
- LOEUF 0.68 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.27 · 32 PDB
- Residue 377
- an α-helix
Similar variants
- SLC18A2 p.Pro387Leu Pathogenic/Likely pathogenic ★★ same type
- SLC18A2 c.834+6C>T Uncertain significance ★★ same type
- SLC18A2 p.Ala164Val Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Ala425Val Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Arg17Cys Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Gly448Glu Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Ile339Val Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Leu260Val 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/slc18a2-p-phe377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown