SEC63 p.Glu290=
c.870G>A · rs1248181773 · VCV2806826
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, nfe)
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 -0.42 | GERP -1.3, phastCons 0.064 |
| Overall | ||
| CADD | 5.642 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
European (non-Finnish) · 13/1,179,380 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.000806%
13/1,613,260 alleles · very rare
exomes 12/1,461,118 · genomes 1/152,142 · joint denominator
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
- SEC63
- Protein
- p.Glu290=
- Coding
- c.870G>A
- MANE Select
- NM_007214
- dbSNP
- rs1248181773
- Type
- single nucleotide variant
- Location
- chr6:107906539 (GRCh38)
- Gene constraint
- LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.71
- Residue 290
- a UniProt-annotated variant site (in pcld2); the sec63 1 domain
Similar variants
- SEC63 c.452+1G>A Pathogenic/Likely pathogenic ★★ same type
- SEC63 c.625-2A>G Likely pathogenic ★★ same type
- SEC63 c.733+1G>A Pathogenic ★★ same type
- SEC63 p.Arg239Ter Pathogenic/Likely pathogenic ★★ same type
- SEC63 p.Arg622Ter Pathogenic/Likely pathogenic ★★ same type
- SEC63 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same type
- SEC63 p.Ser632Ter Pathogenic/Likely pathogenic ★★ same type
- SEC63 p.Trp58Ter Pathogenic ★★ 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/sec63-p-glu290 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown