SPEG p.Pro750=
c.2250G>A · rs56237719 · VCV771342
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.8%, 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 -6.4 | GERP -3.1 |
| Overall | ||
| CADD | 0.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.8%
Admixed American · 1,655/59,048 alleles
Filtering AF
2.69%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.65%
Overall
0.181%
2,903/1,607,406 alleles · low-frequency
exomes 2,552/1,455,186 · genomes 351/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 2.8% | 36 |
| East Asian | 2.26% | 44 |
| Remaining individualsnot grpmax-eligible | 0.129% | 778 |
| South Asian | 0.0899% | 1,112 |
| African / African-American | 0.0588% | 1,700 |
| Middle Eastern | 0.0506% | 1,977 |
| European (non-Finnish) | 0.00238% | 42,041 |
| Finnishnot grpmax-eligible | 0.00158% | 63,462 |
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
- SPEG
- Protein
- p.Pro750=
- Coding
- c.2250G>A
- MANE Select
- NM_005876
- dbSNP
- rs56237719
- Type
- single nucleotide variant
- Location
- chr2:219451272 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 750
- the ig-like 2 domain
Similar variants
- SPEG p.Pro750Leu Benign/Likely benign ★★ same residue
- SPEG p.Arg1467Ter Likely pathogenic ★★ same type
- SPEG p.Ser131Ter Pathogenic/Likely pathogenic ★★ same type
- SPEG c.3301+5G>A Uncertain significance ★★ same type
- SPEG c.478+5G>A Uncertain significance ★★ same type
- SPEG p.Ala121Thr Uncertain significance ★★ same type
- SPEG p.Ala1249Thr Uncertain significance ★★ ⚠ same type
- SPEG p.Ala1334Val 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/speg-p-pro750 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown