Is PLOD1 p.Arg644= (c.1932C>T) pathogenic?

PLOD1 p.Arg644= (c.1932C>T) is classified Likely benign in PLOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). Very rare (popmax 0.00133%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with PLOD1 p.Arg644= (c.1932C>T)?

PLOD1 p.Arg644= (c.1932C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PLOD1 p.Arg644= (c.1932C>T) in the general population?

PLOD1 p.Arg644= (c.1932C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

PLOD1 p.Arg644=

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.1932C>T · rs11553677 · VCV3231129

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.79	GERP -2.4, phastCons 1
Overall
CADD	12.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Overall 0.000124% 2/1,613,992 alleles · very rare exomes 1/1,461,826 · genomes 1/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,924
European (non-Finnish)	8.47e-05%	1,180,002

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: PLOD1
Protein: p.Arg644=
Coding: c.1932C>T
MANE Select: NM_000302
dbSNP: rs11553677
Type: single nucleotide variant
Location: chr1:11972901 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04
Residue 644: 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 p.Arg644Cys Uncertain significance ★★ ⚠ same residue
PLOD1 p.Arg644His Uncertain significance ★ ⚠ same residue
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

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-arg644 (accessed [today's date]).

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