Is LOX p.Ser178= (c.534T>C) pathogenic?

LOX p.Ser178= (c.534T>C) is classified Benign/Likely benign in LOX (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0264%, nfe); Associated with aortic aneurysm, familial thoracic 10.

What condition is associated with LOX p.Ser178= (c.534T>C)?

LOX p.Ser178= (c.534T>C) is associated with aortic aneurysm, familial thoracic 10 (ClinVar).

How common is LOX p.Ser178= (c.534T>C) in the general population?

LOX p.Ser178= (c.534T>C) is ultra-rare (popmax 0.0264%, nfe) (gnomAD).

LOX p.Ser178=

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.534T>C · rs144768703 · VCV496152

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, nfe)

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 -2.4	GERP -3.6
Overall
CADD	6.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0264% European (non-Finnish) · 311/1,180,006 alleles

Filtering AF 0.0239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0271% 438/1,614,088 alleles · ultra-rare exomes 393/1,461,770 · genomes 45/152,318 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.186%	537
European (non-Finnish)grpmax	0.0264%	3,794
Remaining individualsnot grpmax-eligible	0.008%	12,501
African / African-American	0.00266%	37,529
Admixed American	0.00167%	60,032

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser178=
Coding: c.534T>C
MANE Select: NM_002317
dbSNP: rs144768703
Type: single nucleotide variant
Location: chr5:122077452 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06

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.Ser178Cys Uncertain significance ★ ⚠ same residue
LOX p.Ser178Pro Conflicting classifications of pathogenicity ★ ⚠ 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.Arg68Pro 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-ser178 (accessed [today's date]).

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