PCSK6 p.Asp309=
c.927C>T · rs757404163 · VCV750103
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.3 | GERP -5.3 |
| Overall | ||
| CADD | 2.496 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
Admixed American · 14/60,032 alleles
Filtering AF
0.0141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0112%
Overall
0.00161%
26/1,613,968 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0233% | 4,288 |
| African / African-American | 0.00533% | 18,765 |
| South Asian | 0.0022% | 45,534 |
| European (non-Finnish) | 0.000509% | 196,642 |
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
- PCSK6
- Protein
- p.Asp309=
- Coding
- c.927C>T
- MANE Select
- NM_002570
- dbSNP
- rs757404163
- Type
- single nucleotide variant
- Location
- chr15:101398473 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.84
- Residue 309
- the peptidase s8 domain
Similar variants
- PCSK6 c.1533-6C>G Benign ★★ same type
- PCSK6 p.Ala867Val Likely benign ★★ same type
- PCSK6 p.Pro455= Benign ★★ same type
- PCSK6 p.Thr964Met Likely benign ★★ same type
- PCSK6 p.Asn161= Conflicting classifications of pathogenicity ★ same type
- PCSK6 p.Pro3Leu Uncertain significance ★ ⚠ same type
- PCSK6 p.Ala33= Likely benign ★ same type
- PCSK6 p.Ala529= Likely benign ★ 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/pcsk6-p-asp309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown