SMPD2 p.Ser75=
c.225C>T · VCV3799238
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 -3.5 |
| Overall | ||
| CADD | 9.312 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,992 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.00167%
27/1,613,668 alleles · very rare
exomes 26/1,461,470 · genomes 1/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,996 |
| East Asian | 0.00223% | 44,894 |
| European (non-Finnish) | 0.00178% | 56,175 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| African / African-American | 0.00133% | 74,926 |
| South Asian | 0.0011% | 91,078 |
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
- SMPD2
- Protein
- p.Ser75=
- Coding
- c.225C>T
- MANE Select
- NM_003080
- Type
- single nucleotide variant
- Location
- chr6:109441974 (GRCh38)
- Gene constraint
- LOEUF 1.046 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.22 · 1 PDB
Similar variants
- SMPD2 p.Ala132Thr Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala200Thr Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala309Thr Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala327Thr Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala327Val Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala368Val Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala370Thr Uncertain significance ★ ⚠ same type
- SMPD2 p.Ala396Val 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/smpd2-p-ser75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown