SMPD4 p.Pro799=
c.2397A>G · VCV4956725
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0377%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.045 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.22 | phastCons 0.91 |
| Overall | ||
| CADD | 4.867 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0377%
South Asian · 32/84,846 alleles
Filtering AF
0.0344%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0332%
Overall
0.033%
515/1,560,472 alleles · ultra-rare
exomes 463/1,408,214 · genomes 52/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0377% | 2,651 |
| European (non-Finnish) | 0.0374% | 2,676 |
| Remaining individualsnot grpmax-eligible | 0.0298% | 3,358 |
| Admixed American | 0.027% | 3,706 |
| Finnishnot grpmax-eligible | 0.025% | 3,996 |
| Middle Eastern | 0.0192% | 5,198 |
| African / African-American | 0.00407% | 24,545 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00348% | 28,724 |
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
- SMPD4
- Protein
- p.Pro799=
- Coding
- c.2397A>G
- MANE Select
- NM_017951
- Type
- single nucleotide variant
- Location
- chr2:130152642 (GRCh38)
- Gene constraint
- LOEUF 0.769 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01
- Residue 799
- a UniProt-annotated variant site (in nedmaba); a UniProt-annotated variant site (in nedmaba; uncertain significance)
Similar variants
- SMPD4 c.1290-9G>A Pathogenic/Likely pathogenic ★★ same type
- SMPD4 c.345+1G>T Pathogenic ★★ same type
- SMPD4 p.Arg502Ter Pathogenic/Likely pathogenic ★★ same type
- SMPD4 p.Arg757Trp Uncertain significance ★★ ⚠ same type
- SMPD4 p.Gln382Glu Uncertain significance ★★ ⚠ same type
- SMPD4 p.Gln722Ter Uncertain significance ★★ same type
- SMPD4 p.Ile82Val Uncertain significance ★★ ⚠ same type
- SMPD4 c.1097+27A>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/smpd4-p-pro799 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown