Is LOX p.Ala84= (c.252C>T) pathogenic?

LOX p.Ala84= (c.252C>T) is classified Likely benign in LOX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-30). Very rare (popmax 0.00532%, nfe); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with LOX p.Ala84= (c.252C>T)?

LOX p.Ala84= (c.252C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is LOX p.Ala84= (c.252C>T) in the general population?

LOX p.Ala84= (c.252C>T) is very rare (popmax 0.00532%, nfe) (gnomAD).

LOX p.Ala84=

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.252C>T · rs770237850 · VCV1792663

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00532%, nfe)

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 1.8	GERP -0.24, phastCons 0.95
Overall
CADD	10.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00532% European (non-Finnish) · 62/1,164,738 alleles

Filtering AF 0.00424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00385%

Overall 0.00413% 65/1,574,680 alleles · very rare exomes 62/1,422,516 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00532%	18,786
Remaining individualsnot grpmax-eligible	0.00327%	30,575
South Asian	0.00114%	87,862

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: LOX
Protein: p.Ala84=
Coding: c.252C>T
MANE Select: NM_002317
dbSNP: rs770237850
Type: single nucleotide variant
Location: chr5:122077734 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06
Residue 84: the 'disordered' region

Full LOX 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

LOX p.Ala84Ser Uncertain significance ★ ⚠ same residue
LOX p.Met298Arg Pathogenic/Likely pathogenic ★★ same condition
LOX p.Trp42Ter Pathogenic/Likely pathogenic ★★ same condition
LOX p.Arg98Ser Uncertain significance ★★ ⚠ same condition
LOX p.Val216Glu Uncertain significance ★★ ⚠ same condition
LOX c.631+10C>T Benign/Likely benign ★★ same condition
LOX p.Arg158Gln Benign ★★ same condition
LOX p.Gln45His Conflicting classifications of pathogenicity ★ ⚠ 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/lox-p-ala84 (accessed [today's date]).

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