Is PLOD3 p.Val44fs (c.131_132del) pathogenic?

PLOD3 p.Val44fs (c.131132del) is classified Pathogenic in PLOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-27). Very rare (popmax 8.48e-05%, nfe).

How common is PLOD3 p.Val44fs (c.131_132del) in the general population?

PLOD3 p.Val44fs (c.131_132del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PLOD3 p.Val44fs

c.131_132del · rs2535179077 · VCV2859808

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-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 2 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,530 alleles

Overall 6.2e-05% 1/1,613,572 alleles · very rare exomes 1/1,461,282 · genomes 0/152,290 · 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.Val44fs
Coding: c.131_132del
MANE Select: NM_001084
dbSNP: rs2535179077
Type: Microsatellite
Location: chr7:101216764 (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 44: the 'required for glycosyltransferase activity' region; a β-strand; a binding site

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

Similar variants

PLOD3 p.Val44= Likely benign ★ same residue
PLOD3 p.Asp191del Uncertain significance ★★ same type
PLOD3 p.Arg162fs Pathogenic ★ same type
PLOD3 p.Ser637fs Pathogenic ★ same type
PLOD3 p.Asn335del Uncertain significance ★ same type
PLOD3 p.His668del Uncertain significance ★ same type
PLOD3 p.Leu664fs Uncertain significance ★ same type
PLOD3 p.Val699fs 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-val44fs (accessed [today's date]).

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