Is PLOD2 p.Ser299fs (c.893dup) pathogenic?

PLOD2 p.Ser299fs (c.893dup) is classified Pathogenic in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-05). Very rare (popmax 8.52e-05%, nfe).

How common is PLOD2 p.Ser299fs (c.893dup) in the general population?

PLOD2 p.Ser299fs (c.893dup) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

PLOD2 p.Ser299fs

c.893dup · rs2473262415 · VCV2826246

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, 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 9 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,174,088 alleles

Overall 6.22e-05% 1/1,607,002 alleles · very rare exomes 1/1,455,154 · genomes 0/151,848 · 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: PLOD2
Protein: p.Ser299fs
Coding: c.893dup
MANE Select: NM_182943
dbSNP: rs2473262415
Type: Duplication
Location: chr3:146088697 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 299: a UniProt-annotated variant site (in brks2; likely pathogenic)

Full PLOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLOD2 p.Cys4fs Pathogenic/Likely pathogenic ★★ same type
PLOD2 p.Val523fs Pathogenic ★★ same type
PLOD2 c.339-22dup Benign ★★ same type
PLOD2 p.Gly301fs Likely pathogenic ★ same type
PLOD2 p.Gly534fs Likely pathogenic ★ same type
PLOD2 p.Phe118fs Likely pathogenic ★ same type
PLOD2 p.Ser621_Gly622insSer Uncertain significance ★ same type
PLOD2 c.1006-4dup 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/plod2-p-ser299fs (accessed [today's date]).

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