Is PLOD3 p.Pro20fs (c.59del) pathogenic?

PLOD3 p.Pro20fs (c.59del) is classified Pathogenic in PLOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). Very rare (popmax 0.000178%, nfe).

How common is PLOD3 p.Pro20fs (c.59del) in the general population?

PLOD3 p.Pro20fs (c.59del) is very rare (popmax 0.000178%, nfe) (gnomAD).

PLOD3 p.Pro20fs

c.59del · rs1269424201 · VCV2705859

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000178%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.083	GERP -4, phastCons 0.001
Region caveats
Repeat context	tandem	(GCAGGCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000178% European (non-Finnish) · 2/1,124,454 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000134% 2/1,496,712 alleles · very rare exomes 2/1,344,694 · genomes 0/152,018 · joint denominator

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.Pro20fs
Coding: c.59del
MANE Select: NM_001084
dbSNP: rs1269424201
Type: Deletion
Location: chr7:101217216 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.80 · 18 PDB

Full PLOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLOD3 p.Pro20Ala Uncertain significance ★ ⚠ same residue
PLOD3 c.183_201+9del Likely pathogenic ★ same type
PLOD3 p.Glu660fs Pathogenic ★ same type
PLOD3 p.Leu289fs Pathogenic ★ same type
PLOD3 c.339-11_339-3del Uncertain significance ★ same type
PLOD3 p.Leu722fs Uncertain significance ★ same type
PLOD3 c.1005+16del Likely benign ★ same type
PLOD3 c.1006-3del Likely benign ★ 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-pro20fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown