PLOD2 p.His339=
c.1017T>C · rs776354477 · VCV2419258
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0207%, nfe)
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 5.3 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 10.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0207%
European (non-Finnish) · 226/1,091,376 alleles
Filtering AF
0.0184%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0176%
Overall
0.0161%
242/1,501,742 alleles · ultra-rare
exomes 229/1,349,794 · genomes 13/151,948 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0207% | 4,829 |
| Remaining individualsnot grpmax-eligible | 0.0138% | 7,267 |
| Admixed American | 0.0106% | 9,419 |
| African / African-American | 0.00138% | 72,296 |
| South Asian | 0.00121% | 82,778 |
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.His339=
- Coding
- c.1017T>C
- MANE Select
- NM_182943
- dbSNP
- rs776354477
- Type
- single nucleotide variant
- Location
- chr3:146086897 (GRCh38)
- Gene constraint
- LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.63
- Residue 339
- 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-his339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown