PLOD2 p.Phe378=
c.1134T>C · VCV3352852
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, nfe)
Conditions
1
PLOD2-related disorder
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 4 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 9.629 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
European (non-Finnish) · 76/1,137,610 alleles
Filtering AF
0.00547%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.005%
Overall
0.00523%
82/1,567,040 alleles · very rare
exomes 80/1,414,934 · genomes 2/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00668% | 14,969 |
| Admixed American | 0.00501% | 19,965 |
| Remaining individualsnot grpmax-eligible | 0.00492% | 20,313 |
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
- Protein
- p.Phe378=
- Coding
- c.1134T>C
- MANE Select
- NM_182943
- Type
- single nucleotide variant
- Location
- chr3:146085267 (GRCh38)
- Gene constraint
- LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.63
- Residue 378
- a UniProt-annotated variant site (in brks2; likely pathogenic)
Disease context
PLOD2-related disorder
Similar variants
- PLOD2 p.Pro324Leu Uncertain significance ★★ ⚠ same condition
- PLOD2 c.2122-2A>G Conflicting classifications of pathogenicity ★ same condition
- PLOD2 p.Lys94Glu Uncertain significance same condition
- PLOD2 c.1995+7A>G Likely benign same condition
- PLOD2 p.Val107fs Likely pathogenic same condition
- PLOD2 c.1500+1G>T Pathogenic/Likely pathogenic ★★ same type
- PLOD2 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same type
- PLOD2 p.Arg473Ter Pathogenic ★★ 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/plod2-p-phe378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown