SMPD4 p.Pro548=
c.1644C>T · rs142500439 · VCV2651357
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.509%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.153 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.6 | |
| Overall | ||
| CADD | 2.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.509%
African / African-American · 381/74,874 alleles
Filtering AF
0.467%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.45%
Overall
0.028%
450/1,605,486 alleles · rare
exomes 215/1,453,154 · genomes 235/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.509% | 197 |
| Middle Eastern | 0.0653% | 1,531 |
| Admixed American | 0.0468% | 2,137 |
| Remaining individualsnot grpmax-eligible | 0.029% | 3,446 |
| European (non-Finnish) | 0.0017% | 58,769 |
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.Pro548=
- Coding
- c.1644C>T
- MANE Select
- NM_017951
- dbSNP
- rs142500439
- Type
- single nucleotide variant
- Location
- chr2:130154292 (GRCh38)
- Gene constraint
- LOEUF 0.769 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01
- Residue 548
- a UniProt-annotated variant site (in nedmaba)
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-pro548 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown