SPNS2 p.Phe415=
c.1245C>T · rs138391650 · VCV3040671
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.69%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.4 | GERP -3.1 |
| Overall | ||
| CADD | 4.139 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.69%
African / African-American · 517/74,912 alleles
Filtering AF
0.641%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.621%
Overall
0.0543%
874/1,608,720 alleles · rare
exomes 559/1,456,542 · genomes 315/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.69% | 145 |
| Middle Eastern | 0.116% | 865 |
| Remaining individualsnot grpmax-eligible | 0.0914% | 1,094 |
| Admixed American | 0.0822% | 1,217 |
| European (non-Finnish) | 0.0197% | 5,078 |
| South Asian | 0.00881% | 11,347 |
| East Asian | 0.0067% | 14,936 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,474 |
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
- SPNS2
- Protein
- p.Phe415=
- Coding
- c.1245C>T
- MANE Select
- NM_001124758
- dbSNP
- rs138391650
- Type
- single nucleotide variant
- Location
- chr17:4533399 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.85 · 18 PDB
- Residue 415
- an α-helix
Similar variants
- SPNS2 p.Ala401Thr Uncertain significance ★★ ⚠ same type
- SPNS2 p.Ala545Thr Uncertain significance ★★ ⚠ same type
- SPNS2 c.1279-152G>A Benign ★★ same type
- SPNS2 c.1344+66C>T Benign ★★ same type
- SPNS2 c.1345-58A>G Benign ★★ same type
- SPNS2 c.1345-89G>A Benign ★★ same type
- SPNS2 c.1443+27C>A Benign ★★ same type
- SPNS2 c.1443+28A>G Benign ★★ 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/spns2-p-phe415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown