PLD3 p.Val232=
c.696G>C · rs139897683 · VCV2182805
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, nfe)
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 2.4 | GERP -0.88, phastCons 1 |
| Overall | ||
| CADD | 9.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
European (non-Finnish) · 270/1,179,628 alleles
Filtering AF
0.0206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.0176%
284/1,613,272 alleles · ultra-rare
exomes 267/1,461,138 · genomes 17/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0229% | 4,369 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,922 |
| African / African-American | 0.00401% | 24,965 |
| Admixed American | 0.00333% | 29,994 |
| Finnishnot grpmax-eligible | 0.00314% | 31,883 |
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
- PLD3
- Protein
- p.Val232=
- Coding
- c.696G>C
- MANE Select
- NM_012268
- dbSNP
- rs139897683
- Type
- single nucleotide variant
- Location
- chr19:40371690 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.15 · 7 PDB
- Residue 232
- a UniProt-annotated variant site (found in patients with alzheimer disease; uncertain significance; does not reduce either amyloid-beta levels or app expression; no effect on protein maturation or trafficking to lysosomes; partial loss of dimer formation; decreased or complete loss of exonuclease activity toward mitochondrial cpg-rich ssdna fragments resulting in dna build-up in the endolysosomal compartment, increased tlr9 pro-inflammatory signaling and increased mitophagy; decreased exonuclease activity toward rna substrate; decreased (s,s)- bmp synthase activity); a β-strand
Similar variants
- PLD3 p.Val232Met Benign/Likely benign ★★ same residue
- PLD3 p.Ala114Val Uncertain significance ★★ ⚠ same type
- PLD3 p.Arg375Trp Uncertain significance ★★ ⚠ same type
- PLD3 p.Arg413His Uncertain significance ★★ ⚠ same type
- PLD3 p.Arg424Ser Uncertain significance ★★ ⚠ same type
- PLD3 p.Arg457Gln Uncertain significance ★★ ⚠ same type
- PLD3 p.Arg488His Uncertain significance ★★ ⚠ same type
- PLD3 p.Asn313Asp 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/pld3-p-val232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown