PLCD1 p.Ala290=
c.870A>C · rs1575347694 · VCV738969
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -6.7 | GERP -4.2 |
| Overall | ||
| CADD | 0.411 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,052 alleles
Filtering AF
0.0221%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0212%
Overall
0.0197%
316/1,606,160 alleles · ultra-rare
exomes 316/1,453,884 · genomes 0/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,026 |
| European (non-Finnish) | 0.0245% | 4,086 |
| Remaining individualsnot grpmax-eligible | 0.0225% | 4,445 |
| South Asian | 0.0077% | 12,992 |
| African / African-American | 0.00667% | 14,991 |
| East Asian | 0.00223% | 44,846 |
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
- PLCD1
- Protein
- p.Ala290=
- Coding
- c.870A>C
- MANE Select
- NM_006225
- dbSNP
- rs1575347694
- Type
- single nucleotide variant
- Location
- chr3:38010483 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.31
Similar variants
- PLCD1 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same type
- PLCD1 p.Arg138His Uncertain significance ★★ ⚠ same type
- PLCD1 p.Arg476His Uncertain significance ★★ ⚠ same type
- PLCD1 p.Arg60Gln Uncertain significance ★★ ⚠ same type
- PLCD1 p.Pro417Arg Uncertain significance ★★ ⚠ same type
- PLCD1 p.Ser650Ala Uncertain significance ★★ ⚠ same type
- PLCD1 c.1607-42C>T Benign ★★ same type
- PLCD1 c.1724-186C>G 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/plcd1-p-ala290 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown