PLCD1 p.Ala249=
c.747G>A · rs531975960 · VCV3050810
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, amr)
Conditions
1
PLCD1-related disorder
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 -12 | GERP -3.8 |
| Overall | ||
| CADD | 0.102 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
Admixed American · 27/60,026 alleles
Filtering AF
0.0317%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0273%
Overall
0.00465%
75/1,611,266 alleles · ultra-rare
exomes 48/1,458,906 · genomes 27/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.045% | 2,223 |
| South Asian | 0.0319% | 3,137 |
| East Asian | 0.0134% | 7,479 |
| African / African-American | 0.008% | 12,499 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,776 |
| European (non-Finnish) | 0.000339% | 294,993 |
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.Ala249=
- Coding
- c.747G>A
- MANE Select
- NM_006225
- dbSNP
- rs531975960
- Type
- single nucleotide variant
- Location
- chr3:38011257 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.31
Disease context
PLCD1-related disorder
Similar variants
- PLCD1 p.Ala249Val Uncertain significance ★ ⚠ same residue
- PLCD1 p.Ala553Thr Conflicting classifications of pathogenicity ⚠ same condition
- PLCD1 p.Glu462Lys Uncertain significance ⚠ same condition
- PLCD1 c.429-5C>T Likely benign same condition
- PLCD1 c.993-4G>A Likely benign same condition
- PLCD1 c.993-5C>T Likely benign same condition
- PLCD1 p.His546= Likely benign same condition
- PLCD1 p.Lys49= Likely benign same condition
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-ala249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown