PLOD2 c.*759T>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.046%, amr)
Conditions
1
Bruck syndrome 2
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 0.23 | GERP -3.1, phastCons 0.018 |
| Non-coding constraint | Z 0.01 | 1 kb window · o/e 1.00 · regional · uncalibrated |
| Overall | ||
| CADD | 2.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.046%
Admixed American · 7/15,212 alleles
Filtering AF
0.0216%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0153%
Overall
0.00722%
11/152,356 alleles · ultra-rare
exomes 0/310 · genomes 11/152,046 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.046% | 2,173 |
| European (non-Finnish) | 0.00589% | 16,973 |
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
- PLOD2
- Coding
- c.*759T>C
- MANE Select
- NM_182943
- dbSNP
- rs192883327
- Type
- single nucleotide variant
- Location
- chr3:146069958 (GRCh38)
- Gene constraint
- LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.63
Similar variants
- PLOD2 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same condition
- PLOD2 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
- PLOD2 p.Arg680Ter Pathogenic/Likely pathogenic ★★ same condition
- PLOD2 c.-170C>G Uncertain significance ★★ same condition
- PLOD2 p.Ala415Val Uncertain significance ★★ ⚠ same condition
- PLOD2 p.Arg619Cys Uncertain significance ★★ ⚠ same condition
- PLOD2 p.Arg648Trp Uncertain significance ★★ ⚠ same condition
- PLOD2 p.Asp102Glu Uncertain significance ★★ ⚠ 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/plod2-c-star-759t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown