Is LOX p.Ser56= (c.168C>T) pathogenic?

LOX p.Ser56= (c.168C>T) is classified Likely benign in LOX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-17). Very rare (popmax 0.00193%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LOX p.Ser56= (c.168C>T)?

LOX p.Ser56= (c.168C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LOX p.Ser56= (c.168C>T) in the general population?

LOX p.Ser56= (c.168C>T) is very rare (popmax 0.00193%, amr) (gnomAD).

LOX p.Ser56=

c.168C>T · rs1036096526 · VCV1778107

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00193%, amr)

Conditions

Cardiovascular phenotype

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 0.94, phastCons 1
Overall
CADD	12.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00193% Admixed American · 1/51,706 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000266%

Overall 0.000644% 10/1,551,964 alleles · very rare exomes 6/1,399,842 · genomes 4/152,122 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00193%	51,706
European (non-Finnish)	0.00078%	128,222

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.Ser56=
Coding: c.168C>T
MANE Select: NM_002317
dbSNP: rs1036096526
Type: single nucleotide variant
Location: chr5:122077818 (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

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

Similar variants

LOX p.Ser56Arg Uncertain significance ★ ⚠ same residue
LOX p.Arg281Ter Pathogenic/Likely pathogenic ★★ same condition
LOX p.Gly202Ter Pathogenic/Likely pathogenic ★★ same condition
LOX c.1247+1G>A Uncertain significance ★★ same condition
LOX p.Ala100Thr Uncertain significance ★★ ⚠ same condition
LOX p.Ala107Thr Uncertain significance ★★ ⚠ same condition
LOX p.Ala147Thr Uncertain significance ★★ ⚠ same condition
LOX p.Arg162Cys 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-ser56 (accessed [today's date]).

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