Is LOX p.Arg68= (c.204C>T) pathogenic?

LOX p.Arg68= (c.204C>T) is classified Benign/Likely benign in LOX (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-28). Rare (popmax 0.945%, afr); Associated with aortic aneurysm, familial thoracic 10.

What condition is associated with LOX p.Arg68= (c.204C>T)?

LOX p.Arg68= (c.204C>T) is associated with aortic aneurysm, familial thoracic 10 (ClinVar).

How common is LOX p.Arg68= (c.204C>T) in the general population?

LOX p.Arg68= (c.204C>T) is rare (popmax 0.945%, afr) (gnomAD).

LOX p.Arg68=

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.204C>T · rs201057539 · VCV785135

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.945%, afr)

Conditions

aortic aneurysm, familial thoracic 10

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 0.36	GERP -2, phastCons 0.99
Overall
CADD	7.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.945% African / African-American · 693/73,300 alleles

Filtering AF 0.887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.864%

Overall 0.0507% 785/1,548,990 alleles · rare exomes 372/1,396,908 · genomes 413/152,082 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.945%	106
Middle Eastern	0.101%	986
Remaining individualsnot grpmax-eligible	0.0614%	1,628
Admixed American	0.0602%	1,661
South Asian	0.00236%	42,445
European (non-Finnish)	0.00139%	71,986

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.Arg68=
Coding: c.204C>T
MANE Select: NM_002317
dbSNP: rs201057539
Type: single nucleotide variant
Location: chr5:122077782 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06
Residue 68: the 'disordered' region

Full LOX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aortic aneurysm, familial thoracic 10 — 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.Arg68Pro Uncertain significance ★★ ⚠ same residue
LOX p.Arg68Leu Uncertain significance ★ ⚠ same residue
LOX c.1035+1G>A Pathogenic/Likely pathogenic ★★ same condition
LOX p.Met298Arg Pathogenic/Likely pathogenic ★★ same condition
LOX p.Trp42Ter Pathogenic/Likely pathogenic ★★ same condition
LOX p.Tyr227Ter Pathogenic/Likely pathogenic ★★ same condition
LOX p.Arg122Cys Uncertain significance ★★ ⚠ same condition
LOX p.Arg88Ser 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/lox-p-arg68 (accessed [today's date]).

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