PLOD3 p.Ser166=
c.498T>C · rs909145551 · VCV1899646
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00271%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.36 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.2 |
| Overall | ||
| CADD | 9.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
European (non-Finnish) · 32/1,179,998 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00204%
33/1,613,880 alleles · very rare
exomes 31/1,461,822 · genomes 2/152,058 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00271% | 36,875 |
| Admixed American | 0.00167% | 59,976 |
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
- PLOD3
- Protein
- p.Ser166=
- Coding
- c.498T>C
- MANE Select
- NM_001084
- dbSNP
- rs909145551
- Type
- single nucleotide variant
- Location
- chr7:101216167 (GRCh38)
- Gene constraint
- LOEUF 0.925 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.80 · 18 PDB
- Residue 166
- the 'required for glycosyltransferase activity' region; a β-strand
Similar variants
- PLOD3 c.1359-1G>C Likely pathogenic ★★ same type
- PLOD3 p.Arg452Ter Pathogenic ★★ same type
- PLOD3 p.Tyr630Ter Pathogenic/Likely pathogenic ★★ same type
- PLOD3 c.338+6G>C Uncertain significance ★★ same type
- PLOD3 p.Ala371Val Uncertain significance ★★ ⚠ same type
- PLOD3 p.Ala431Thr Uncertain significance ★★ ⚠ same type
- PLOD3 p.Ala59Val Uncertain significance ★★ ⚠ same type
- PLOD3 p.Ala646Val 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/plod3-p-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown