PKD1 p.Ser286=
c.858T>C · rs886038372 · VCV257023
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00187%, nfe)
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 0.24 | GERP -0.69, phastCons 0.3 |
| Overall | ||
| CADD | 9.322 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00187%
European (non-Finnish) · 22/1,174,164 alleles
Filtering AF
0.00123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.00144%
23/1,597,834 alleles · very rare
exomes 21/1,445,616 · genomes 2/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00187% | 53,371 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,754 |
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
- PKD1
- Protein
- p.Ser286=
- Coding
- c.858T>C
- MANE Select
- NM_001009944
- dbSNP
- rs886038372
- Type
- single nucleotide variant
- Location
- chr16:2118134 (GRCh38)
- Gene constraint
- LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 286
- the pkd 1 domain; a β-strand
Similar variants
- PKD1 p.Ser286Cys Uncertain significance ★ ⚠ same residue
- PKD1 p.Ser286_Gly287insTer Pathogenic ★ same residue
- PKD1 p.Ser286_Gly287insTrp Uncertain significance ★ same residue
- PKD1 c.10619-2A>G Pathogenic ★★ same type
- PKD1 c.10821+1G>A Pathogenic/Likely pathogenic ★★ same type
- PKD1 c.10821+2T>G Pathogenic/Likely pathogenic ★★ same type
- PKD1 c.11017-10C>A Pathogenic/Likely pathogenic ★★ same type
- PKD1 c.11017-25A>C Likely 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/pkd1-p-ser286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown