Is PLOD1 p.Ile294= (c.882C>T) pathogenic?

PLOD1 p.Ile294= (c.882C>T) is classified Conflicting classifications of pathogenicity in PLOD1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-23). Very rare (popmax 0.00549%, sas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with PLOD1 p.Ile294= (c.882C>T)?

PLOD1 p.Ile294= (c.882C>T) is associated with familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, kyphoscoliotic type 1 (ClinVar).

How common is PLOD1 p.Ile294= (c.882C>T) in the general population?

PLOD1 p.Ile294= (c.882C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

PLOD1 p.Ile294=

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.882C>T · rs747668784 · VCV618331

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 -5.6	GERP -4.8
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,044 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00235% 38/1,613,906 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,209
Admixed American	0.00333%	29,991
African / African-American	0.00267%	37,499
European (non-Finnish)	0.00237%	42,141
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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.Ile294=
Coding: c.882C>T
MANE Select: NM_000302
dbSNP: rs747668784
Type: single nucleotide variant
Location: chr1:11958554 (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 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
PLOD1 c.168+1G>T Likely pathogenic ★★ same condition
PLOD1 c.1903-2A>G Likely pathogenic ★★ same condition
PLOD1 c.467-2A>G 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-ile294 (accessed [today's date]).

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