SEC63 p.Thr227=
c.681A>G · rs138393465 · VCV2977452
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.084%, afr)
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 -0.045 | GERP -2.8, phastCons 0.91 |
| Overall | ||
| CADD | 8.437 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.084%
African / African-American · 63/74,988 alleles
Filtering AF
0.0674%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0613%
Overall
0.00421%
68/1,613,538 alleles · ultra-rare
exomes 36/1,461,390 · genomes 32/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.084% | 1,190 |
| Admixed American | 0.00334% | 29,983 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,247 |
| European (non-Finnish) | 8.48e-05% | 1,179,619 |
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.Thr227=
- Coding
- c.681A>G
- MANE Select
- NM_007214
- dbSNP
- rs138393465
- Type
- single nucleotide variant
- Location
- chr6:107908979 (GRCh38)
- Gene constraint
- LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.71
- Residue 227
- 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-thr227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown