Is PLOD1 p.Asp491= (c.1473T>C) pathogenic?

PLOD1 p.Asp491= (c.1473T>C) is classified Likely benign in PLOD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-13). Rare (popmax 0.161%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with PLOD1 p.Asp491= (c.1473T>C)?

PLOD1 p.Asp491= (c.1473T>C) is associated with familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, kyphoscoliotic type 1 (ClinVar).

How common is PLOD1 p.Asp491= (c.1473T>C) in the general population?

PLOD1 p.Asp491= (c.1473T>C) is rare (popmax 0.161%, afr) (gnomAD).

PLOD1 p.Asp491=

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.1473T>C · rs139165192 · VCV459808

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.161%, 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	all four deltas below 0.2 · T>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.8	GERP -4.1
Overall
CADD	1.615	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.161% African / African-American · 120/74,696 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00937% 150/1,600,932 alleles · rare exomes 80/1,448,786 · genomes 70/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.161%	622
Remaining individualsnot grpmax-eligible	0.029%	3,449
Admixed American	0.0183%	5,453
European (non-Finnish)	8.56e-05%	1,168,525

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.Asp491=
Coding: c.1473T>C
MANE Select: NM_000302
dbSNP: rs139165192
Type: single nucleotide variant
Location: chr1:11965482 (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.Asp491Asn Uncertain significance ★★ ⚠ same residue
PLOD1 p.Asp491Tyr Uncertain significance ★★ ⚠ same residue
PLOD1 p.Asp491Gly 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-asp491 (accessed [today's date]).

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