PLOD3 p.Ala648=
c.1944G>A · rs200169267 · VCV1574871
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -8.6 |
| Overall | ||
| CADD | 0.186 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
European (non-Finnish) · 246/1,149,990 alleles
Filtering AF
0.0192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0183%
Overall
0.0162%
253/1,557,226 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0214% | 4,675 |
| Remaining individualsnot grpmax-eligible | 0.00828% | 12,072 |
| African / African-American | 0.00136% | 73,662 |
| South Asian | 0.00118% | 84,472 |
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.Ala648=
- Coding
- c.1944G>A
- MANE Select
- NM_001084
- dbSNP
- rs200169267
- Type
- single nucleotide variant
- Location
- chr7:101206896 (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 648
- a β-strand; the fe2og dioxygenase domain; a UniProt-annotated variant site (in bcard; uncertain significance)
Similar variants
- PLOD3 p.Ala648Val Uncertain significance ★ ⚠ same residue
- 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
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-ala648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown