SPEG p.Pro1773=
c.5319C>T · rs376664998 · VCV1560586
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -2.8 |
| Overall | ||
| CADD | 2.504 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00721%
Overall
0.00502%
81/1,613,880 alleles · ultra-rare
exomes 64/1,461,608 · genomes 17/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| African / African-American | 0.016% | 6,253 |
| South Asian | 0.00769% | 13,010 |
| Admixed American | 0.00666% | 15,008 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| European (non-Finnish) | 0.00458% | 21,852 |
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.Pro1773=
- Coding
- c.5319C>T
- MANE Select
- NM_005876
- dbSNP
- rs376664998
- Type
- single nucleotide variant
- Location
- chr2:219480117 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 1773
- the protein kinase 1 domain
Similar variants
- 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
- SPEG p.Ala154Asp 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-pro1773 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown