PLOD2 p.Pro743=
c.2229T>C · rs78976445 · VCV785068
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.43%, afr)
Conditions
2
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 0.057 | GERP -4.1, phastCons 0.045 |
| Overall | ||
| CADD | 6.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.43%
African / African-American · 1,069/74,824 alleles
Filtering AF
1.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.33%
Overall
0.0815%
1,311/1,609,528 alleles · low-frequency
exomes 659/1,457,556 · genomes 652/151,972 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.43% | 70 |
| Admixed American | 0.132% | 756 |
| Remaining individualsnot grpmax-eligible | 0.119% | 842 |
| Middle Eastern | 0.0331% | 3,024 |
| European (non-Finnish) | 0.00739% | 13,523 |
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.Pro743=
- Coding
- c.2229T>C
- MANE Select
- NM_182943
- dbSNP
- rs78976445
- Type
- single nucleotide variant
- Location
- chr3:146070765 (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.Arg484Cys Uncertain significance ★★ ⚠ same condition
- PLOD2 p.Arg619Cys Uncertain significance ★★ ⚠ same condition
- PLOD2 p.Arg648Trp 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-p-pro743 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown