SPNS2 p.Pro72=
c.216C>T · rs568443260 · VCV3044738
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.85%, 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 -0.58 | GERP -2, phastCons 0.006 |
| Overall | ||
| CADD | 7.946 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.85%
African / African-American · 1,256/68,036 alleles
Filtering AF
1.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.73%
Overall
0.101%
1,492/1,474,560 alleles · low-frequency
exomes 722/1,323,048 · genomes 770/151,512 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.85% | 54 |
| Middle Eastern | 0.184% | 543 |
| Remaining individualsnot grpmax-eligible | 0.154% | 649 |
| Admixed American | 0.136% | 733 |
| European (non-Finnish) | 0.00715% | 13,988 |
| South Asian | 0.00129% | 77,784 |
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.Pro72=
- Coding
- c.216C>T
- MANE Select
- NM_001124758
- dbSNP
- rs568443260
- Type
- single nucleotide variant
- Location
- chr17:4499263 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.85 · 18 PDB
- Residue 72
- the 'disordered' region
Similar variants
- SPNS2 p.Pro72Arg Uncertain significance ★ ⚠ same residue
- 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
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-pro72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown