SPHK2 p.Ser245=
c.735G>C · rs746600744 · VCV739788
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00335%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.3 |
| Overall | ||
| CADD | 0.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00335%
South Asian · 3/89,538 alleles
Filtering AF
0.00089%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000447%
Overall
0.000251%
4/1,594,382 alleles · very rare
exomes 4/1,442,182 · genomes 0/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00335% | 29,846 |
| African / African-American | 0.00134% | 74,576 |
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.Ser245=
- Coding
- c.735G>C
- MANE Select
- NM_020126
- dbSNP
- rs746600744
- Type
- single nucleotide variant
- Location
- chr19:48628048 (GRCh38)
- Gene constraint
- LOEUF 0.934 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.65
- Residue 245
- the dagkc domain; a binding site
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-ser245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown