Is LOX p.Ser247Arg (c.739A>C) pathogenic?

LOX p.Ser247Arg (c.739A>C) is classified Uncertain significance in LOX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-28). AlphaMissense: ambiguous (0.4452); Very rare (popmax 0.000508%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LOX p.Ser247Arg (c.739A>C)?

LOX p.Ser247Arg (c.739A>C) is associated with Cardiovascular phenotype, aortic aneurysm, familial thoracic 10 (ClinVar).

How common is LOX p.Ser247Arg (c.739A>C) in the general population?

LOX p.Ser247Arg (c.739A>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about LOX p.Ser247Arg (c.739A>C)?

AlphaMissense predicts ambiguous (score 0.4452) — an in-silico prediction, not a clinical call.

LOX p.Ser247Arg

c.739A>C · rs2152590924 · VCV1516318

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4452	ambiguous
REVEL	0.34	indeterminate
SaProt	LLR -11.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,475 bp · p 0.092 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,179,974 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,716 alleles · very rare

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.Ser247Arg
Coding: c.739A>C
MANE Select: NM_002317
dbSNP: rs2152590924
Type: single nucleotide variant
Location: chr5:122076894 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06
Residue 247: the 'lysyl-oxidase like' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aortic aneurysm, familial thoracic 10

Similar variants

LOX c.1035+1G>A Pathogenic/Likely pathogenic ★★ same condition
LOX p.Arg281Ter Pathogenic/Likely pathogenic ★★ same condition
LOX p.Gly202Ter 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 c.1247+1G>A Uncertain significance ★★ same condition
LOX p.Ala100Thr 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-ser247arg (accessed [today's date]).

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