SPEG p.Pro618=
c.1854C>T · rs990815272 · VCV1645606
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00213%, 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 -0.8 | GERP -2.7 |
| Overall | ||
| CADD | 2.934 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00213%
European (non-Finnish) · 24/1,128,952 alleles
Filtering AF
0.00144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00121%
Overall
0.00166%
25/1,506,176 alleles · very rare
exomes 24/1,353,944 · genomes 1/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00213% | 47,040 |
| Remaining individualsnot grpmax-eligible | 0.00172% | 58,244 |
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.Pro618=
- Coding
- c.1854C>T
- MANE Select
- NM_005876
- dbSNP
- rs990815272
- Type
- single nucleotide variant
- Location
- chr2:219449012 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 618
- the 'disordered' region
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-pro618 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown