Is PLOD1 p.Arg693= (c.2077A>C) pathogenic?

PLOD1 p.Arg693= (c.2077A>C) is classified Likely benign in PLOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with PLOD1 p.Arg693= (c.2077A>C)?

PLOD1 p.Arg693= (c.2077A>C) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PLOD1 p.Arg693= (c.2077A>C) in the general population?

PLOD1 p.Arg693= (c.2077A>C) is absent from gnomAD v4.1 (gnomAD).

PLOD1 p.Arg693=

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.2077A>C · VCV3420942

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 0.51	GERP -3, phastCons 0.015
Overall
CADD	5.941	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.Arg693=
Coding: c.2077A>C
MANE Select: NM_000302
Type: single nucleotide variant
Location: chr1:11974701 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04
Residue 693: the fe2og dioxygenase domain

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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

PLOD1 c.1097+1G>A Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.1471-2A>G Likely pathogenic ★★ same condition
PLOD1 c.1651-2A>G Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.467-2A>G Likely pathogenic ★★ same condition
PLOD1 p.Ala667Thr Likely pathogenic ★★ same condition
PLOD1 p.Gln56Ter Pathogenic ★★ same condition
PLOD1 p.Tyr511Ter Pathogenic ★★ same condition
PLOD1 c.741+4G>C Uncertain significance ★★ 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-arg693 (accessed [today's date]).

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