Is LOX p.Arg88Ser (c.262C>A) pathogenic?

LOX p.Arg88Ser (c.262C>A) is classified Uncertain significance in LOX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-09). AlphaMissense: likely benign (0.1263); Very rare (popmax 0.00179%, amr); Associated with aortic aneurysm, familial thoracic 10.

What condition is associated with LOX p.Arg88Ser (c.262C>A)?

LOX p.Arg88Ser (c.262C>A) is associated with aortic aneurysm, familial thoracic 10 (ClinVar).

How common is LOX p.Arg88Ser (c.262C>A) in the general population?

LOX p.Arg88Ser (c.262C>A) is very rare (popmax 0.00179%, amr) (gnomAD).

What do computational predictors say about LOX p.Arg88Ser (c.262C>A)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

LOX p.Arg88Ser

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.262C>A · rs997637411 · VCV2428718

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00179%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aortic aneurysm, familial thoracic 10

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,475 bp · p 0.092 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00179% Admixed American · 1/55,824 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00035% 5/1,428,718 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00187%	53,598
Admixed Americangrpmax	0.00179%	55,824
European (non-Finnish)	0.000257%	389,222

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.Arg88Ser
Coding: c.262C>A
MANE Select: NM_002317
dbSNP: rs997637411
Type: single nucleotide variant
Location: chr5:122077724 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06
Residue 88: 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.Arg88His 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
LOX p.Asp368Asn 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-arg88ser (accessed [today's date]).

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