SPHK2 p.Pro415=
c.1245C>T · rs370772383 · VCV2650214
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0184%, 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 -0.64 | GERP -2.4 |
| Overall | ||
| CADD | 5.966 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0184%
European (non-Finnish) · 217/1,179,786 alleles
Filtering AF
0.0164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0156%
Overall
0.0146%
236/1,613,224 alleles · ultra-rare
exomes 232/1,461,050 · genomes 4/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0184% | 5,437 |
| Admixed American | 0.015% | 6,662 |
| South Asian | 0.00549% | 18,214 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,813 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,584 |
| African / African-American | 0.00134% | 74,906 |
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
- SPHK2
- Protein
- p.Pro415=
- Coding
- c.1245C>T
- MANE Select
- NM_020126
- dbSNP
- rs370772383
- Type
- single nucleotide variant
- Location
- chr19:48629053 (GRCh38)
- Gene constraint
- LOEUF 0.934 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.65
- Residue 415
- the 'disordered' region
Similar variants
- SPHK2 p.Ala506Ser Benign ★★ same type
- SPHK2 p.Asp530Glu Likely benign ★★ same type
- SPHK2 p.Ala141Ser Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala141Val Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala281Thr Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala295Val Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala367Thr Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala38Thr 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/sphk2-p-pro415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown