PLOD2 p.Leu262=
c.786G>A · rs1002992721 · VCV796621
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00835%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.22 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.12 | GERP 1.4, phastCons 0.49 |
| Overall | ||
| CADD | 4.777 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00835%
Admixed American · 5/59,848 alleles
Filtering AF
0.00324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.000385%
6/1,559,564 alleles · very rare
exomes 3/1,407,706 · genomes 3/151,858 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00835% | 11,970 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,632 |
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.Leu262=
- Coding
- c.786G>A
- MANE Select
- NM_182943
- dbSNP
- rs1002992721
- Type
- single nucleotide variant
- Location
- chr3:146091893 (GRCh38)
- Gene constraint
- LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.63
- Residue 262
- a UniProt-annotated variant site (in brks2; likely pathogenic)
Similar variants
- PLOD2 c.1500+1G>T Pathogenic/Likely pathogenic ★★ same type
- PLOD2 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same type
- PLOD2 p.Arg473Ter Pathogenic ★★ same type
- PLOD2 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same type
- PLOD2 p.Arg680Ter Pathogenic/Likely pathogenic ★★ same type
- PLOD2 c.1232+5T>A Uncertain significance ★★ same type
- PLOD2 c.-170C>G Uncertain significance ★★ same type
- PLOD2 p.Ala415Val 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/plod2-p-leu262 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown