SEC63 p.Leu79=
c.237G>A · rs146134069 · VCV354917
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Conditions
1
polycystic liver disease 2
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 0.32 | GERP -0.28, phastCons 0.98 |
| Overall | ||
| CADD | 7.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,946 alleles
Filtering AF
0.00532%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00485%
Overall
0.00525%
83/1,582,166 alleles · very rare
exomes 75/1,430,068 · genomes 8/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,987 |
| European (non-Finnish) | 0.00651% | 15,352 |
| South Asian | 0.00221% | 45,221 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,374 |
| African / African-American | 0.00135% | 74,210 |
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.Leu79=
- Coding
- c.237G>A
- MANE Select
- NM_007214
- dbSNP
- rs146134069
- Type
- single nucleotide variant
- Location
- chr6:107924920 (GRCh38)
- Gene constraint
- LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.71
- Residue 79
- a UniProt-annotated variant site (in pcld2)
Similar variants
- SEC63 c.452+1G>A Pathogenic/Likely pathogenic ★★ same condition
- SEC63 c.625-2A>G Likely pathogenic ★★ same condition
- SEC63 c.733+1G>A Pathogenic ★★ same condition
- SEC63 p.Arg239Ter Pathogenic/Likely pathogenic ★★ same condition
- SEC63 p.Arg622Ter Pathogenic/Likely pathogenic ★★ same condition
- SEC63 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same condition
- SEC63 p.Ser632Ter Pathogenic/Likely pathogenic ★★ same condition
- SEC63 c.452+3A>G Uncertain significance ★★ same condition
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-leu79 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown