Is PLOD1 p.Arg319= (c.955C>A) pathogenic?

PLOD1 p.Arg319= (c.955C>A) is classified Likely benign in PLOD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-04). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with PLOD1 p.Arg319= (c.955C>A)?

PLOD1 p.Arg319= (c.955C>A) is associated with familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, kyphoscoliotic type 1 (ClinVar).

How common is PLOD1 p.Arg319= (c.955C>A) in the general population?

PLOD1 p.Arg319= (c.955C>A) is absent from gnomAD v4.1 (gnomAD).

PLOD1 p.Arg319=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.955C>A · rs121913550 · VCV3010642

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 0.16	GERP -3.7, phastCons 0.93
Overall
CADD	5.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLOD1
Protein: p.Arg319=
Coding: c.955C>A
MANE Select: NM_000302
dbSNP: rs121913550
Type: single nucleotide variant
Location: chr1:11958627 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04

Full PLOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, kyphoscoliotic type 1

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

PLOD1 p.Arg319Ter Pathogenic ★★ same residue
PLOD1 p.Arg319Gln Uncertain significance ★ ⚠ same residue
PLOD1 p.Arg319Leu Uncertain significance ★ ⚠ same residue
PLOD1 c.1097+1G>A Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.1202+2T>C Likely pathogenic ★★ same condition
PLOD1 c.1470+2T>C Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.1471-2A>G Likely pathogenic ★★ same condition
PLOD1 c.1651-2A>G Pathogenic/Likely pathogenic ★★ same condition

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/plod1-p-arg319 (accessed [today's date]).

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