PCSK7 p.Arg593=
c.1779G>A · VCV3388165
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.136%, 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 1.1 | GERP 0.57, phastCons 1 |
| Overall | ||
| CADD | 14.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.136%
Middle Eastern · 3/2,198 alleles
Filtering AF
0.0372%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.0148%
89/602,212 alleles · rare
exomes 75/469,400 · genomes 14/132,812 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.136% | 733 |
| Remaining individualsnot grpmax-eligible | 0.0446% | 2,241 |
| European (non-Finnish) | 0.0203% | 4,926 |
| Admixed American | 0.00716% | 13,971 |
| South Asian | 0.00368% | 27,198 |
| African / African-American | 0.00204% | 48,966 |
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
- PCSK7
- Protein
- p.Arg593=
- Coding
- c.1779G>A
- MANE Select
- NM_004716
- Type
- single nucleotide variant
- Location
- chr11:117207977 (GRCh38)
- Gene constraint
- LOEUF 0.881 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.92
- Residue 593
- the p/homo b domain
Similar variants
- PCSK7 p.Arg560Gly Uncertain significance ★★ ⚠ same type
- PCSK7 p.Lys545Thr Uncertain significance ★★ ⚠ same type
- PCSK7 c.1786+7C>T Benign ★★ same type
- PCSK7 p.Leu590= Likely benign ★★ same type
- PCSK7 p.Pro777Leu Benign ★★ same type
- PCSK7 c.1691+1G>A Uncertain significance ★ same type
- PCSK7 p.Ala26Thr Uncertain significance ★ ⚠ same type
- PCSK7 p.Ala273Val 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/pcsk7-p-arg593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown