SPTLC2 p.Pro58=
c.174G>A · rs373828710 · VCV513834
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.102%, eas)
Conditions
2
Inborn genetic diseases
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 -6 | GERP -5.6 |
| Overall | ||
| CADD | 3.505 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.102%
East Asian · 46/44,886 alleles
Filtering AF
0.0789%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0706%
Overall
0.007%
113/1,614,186 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.102% | 976 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,683 |
| Admixed American | 0.00666% | 15,006 |
| European (non-Finnish) | 0.00398% | 25,107 |
| South Asian | 0.00329% | 30,361 |
| African / African-American | 0.00266% | 37,528 |
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
- SPTLC2
- Protein
- p.Pro58=
- Coding
- c.174G>A
- MANE Select
- NM_004863
- dbSNP
- rs373828710
- Type
- single nucleotide variant
- Location
- chr14:77597339 (GRCh38)
- Gene constraint
- LOEUF 0.494 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 86.47 · 17 PDB
Similar variants
- SPTLC2 p.Pro58Leu Uncertain significance ★★ ⚠ same residue
- SPTLC2 p.Pro58Arg Uncertain significance ★ ⚠ same residue
- SPTLC2 p.Arg183Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SPTLC2 p.Gly382Val Pathogenic/Likely pathogenic ★★ same condition
- SPTLC2 p.Ser384Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SPTLC2 c.1176+6C>T Uncertain significance ★★ same condition
- SPTLC2 c.756+3A>G Uncertain significance ★★ same condition
- SPTLC2 c.-160A>G 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/sptlc2-p-pro58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown