PKD1 p.Ala3003=
c.9009G>A · rs374619113 · VCV448024
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -4.4 |
| Overall | ||
| CADD | 2.886 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.164%
Middle Eastern · 8/4,882 alleles
Filtering AF
0.0815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0595%
Overall
0.015%
241/1,611,008 alleles · rare
exomes 217/1,458,746 · genomes 24/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.164% | 610 |
| Admixed American | 0.075% | 1,333 |
| Remaining individualsnot grpmax-eligible | 0.0241% | 4,154 |
| European (non-Finnish) | 0.0131% | 7,612 |
| South Asian | 0.00989% | 10,112 |
| African / African-American | 0.00668% | 14,977 |
| Finnishnot grpmax-eligible | 0.00478% | 20,911 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,596 |
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.Ala3003=
- Coding
- c.9009G>A
- MANE Select
- NM_001009944
- dbSNP
- rs374619113
- Type
- single nucleotide variant
- Location
- chr16:2102573 (GRCh38)
- Gene constraint
- LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 3003
- the gain-b domain
Similar variants
- 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
- PKD1 c.11017-25A>G Likely pathogenic ★★ same type
- PKD1 c.11269+1G>C Pathogenic ★★ same type
- PKD1 c.11269+1G>T 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-ala3003 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown