PLCD1 p.Leu44=
c.130T>C · rs61751648 · VCV1244336
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.95 | GERP -3.9 |
| Overall | ||
| CADD | 1.993 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
14.3%
African / African-American · 10,713/74,982 alleles
Filtering AF
14.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14%
Overall
5.93%
95,777/1,613,872 alleles · common
exomes 83,683/1,461,688 · genomes 12,094/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 14.3% | 7 |
| Middle Eastern | 9.44% | 11 |
| South Asian | 9.36% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 9.16% | 11 |
| Remaining individualsnot grpmax-eligible | 6.48% | 15 |
| Finnishnot grpmax-eligible | 5.52% | 18 |
| Amishnot grpmax-eligible | 5.48% | 18 |
| European (non-Finnish) | 5.34% | 19 |
| Admixed American | 4.17% | 24 |
| East Asian | 0.158% | 632 |
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.Leu44=
- Coding
- c.130T>C
- MANE Select
- NM_006225
- dbSNP
- rs61751648
- Type
- single nucleotide variant
- Location
- chr3:38020257 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.31
- Residue 44
- the ph domain; the 'substrate binding' region
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-leu44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown