PLCD1 p.Val122=
c.366G>A · rs72863996 · VCV1228231
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 7.77%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.7 | GERP -4, phastCons 0.004 |
| Overall | ||
| CADD | 6.544 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.77%
African / African-American · 5,826/75,006 alleles
Filtering AF
7.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.53%
Overall
2.03%
32,793/1,613,942 alleles · common
exomes 27,348/1,461,684 · genomes 5,445/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.77% | 13 |
| Ashkenazi Jewishnot grpmax-eligible | 5.64% | 18 |
| Finnishnot grpmax-eligible | 3.73% | 27 |
| Middle Eastern | 2.81% | 36 |
| Remaining individualsnot grpmax-eligible | 2.4% | 42 |
| European (non-Finnish) | 1.63% | 61 |
| Admixed American | 1.57% | 64 |
| South Asian | 1.14% | 88 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| East Asian | 0.0981% | 1,020 |
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.Val122=
- Coding
- c.366G>A
- MANE Select
- NM_006225
- dbSNP
- rs72863996
- Type
- single nucleotide variant
- Location
- chr3:38016553 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.31
- Residue 122
- the ph domain
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-val122 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown