SEC63 p.Leu628=
c.1882T>C · rs149629810 · VCV726395
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, 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 0.42 | GERP -3.5, phastCons 0.009 |
| Overall | ||
| CADD | 1.388 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
Middle Eastern · 1/5,732 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.0018%
29/1,613,190 alleles · ultra-rare
exomes 28/1,461,012 · genomes 1/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0174% | 5,732 |
| Admixed American | 0.005% | 19,997 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,207 |
| European (non-Finnish) | 0.00178% | 56,181 |
| Finnishnot grpmax-eligible | 0.00156% | 63,966 |
| South Asian | 0.0011% | 91,060 |
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.Leu628=
- Coding
- c.1882T>C
- MANE Select
- NM_007214
- dbSNP
- rs149629810
- Type
- single nucleotide variant
- Location
- chr6:107881202 (GRCh38)
- Gene constraint
- LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.71
- Residue 628
- a UniProt-annotated variant site (in pcld2)
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-leu628 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown