PLD2 p.Val546=
c.1638C>T · rs774226127 · VCV724788
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
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 -9.5 | GERP -3.8 |
| Overall | ||
| CADD | 0.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,934 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00904%
Overall
0.00242%
39/1,613,880 alleles · ultra-rare
exomes 30/1,461,686 · genomes 9/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,352 |
| South Asian | 0.00988% | 10,118 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
| European (non-Finnish) | 0.00127% | 78,663 |
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
- PLD2
- Protein
- p.Val546=
- Coding
- c.1638C>T
- MANE Select
- NM_002663
- dbSNP
- rs774226127
- Type
- single nucleotide variant
- Location
- chr17:4816992 (GRCh38)
- Gene constraint
- LOEUF 0.933 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.55 · 6 PDB
- Residue 546
- a β-strand; the 'catalytic' region
Similar variants
- PLD2 c.2010-9C>T Benign ★★ same type
- PLD2 p.Arg330Gln Benign ★★ ⚠ same type
- PLD2 p.Arg490Cys Likely benign ★★ same type
- PLD2 p.Arg553Gln Benign ★★ ⚠ same type
- PLD2 p.His278Tyr Benign ★★ same type
- PLD2 p.Ile860= Benign ★★ same type
- PLD2 p.Thr569Ala Likely benign ★★ same type
- PLD2 p.Ala184Val Uncertain significance ★ ⚠ 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/pld2-p-val546 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown