SPEG p.Phe1763=
c.5289T>C · rs377721845 · VCV791472
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.155%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -2.8 |
| Overall | ||
| CADD | 5.813 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.155%
European (non-Finnish) · 1,829/1,180,010 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.147%
Overall
0.118%
1,900/1,613,818 alleles · rare
exomes 1,809/1,461,700 · genomes 91/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.155% | 645 |
| Remaining individualsnot grpmax-eligible | 0.0816% | 1,225 |
| African / African-American | 0.016% | 6,241 |
| Finnishnot grpmax-eligible | 0.00783% | 12,772 |
| Admixed American | 0.005% | 19,999 |
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.Phe1763=
- Coding
- c.5289T>C
- MANE Select
- NM_005876
- dbSNP
- rs377721845
- Type
- single nucleotide variant
- Location
- chr2:219480087 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 1763
- 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-phe1763 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown