Is AOX1 p.Lys515Arg (c.1544A>G) pathogenic?

AOX1 p.Lys515Arg (c.1544A>G) is classified Uncertain significance in AOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0657); Ultra-rare (popmax 0.0205%, mid).

How common is AOX1 p.Lys515Arg (c.1544A>G) in the general population?

AOX1 p.Lys515Arg (c.1544A>G) is ultra-rare (popmax 0.0205%, mid) (gnomAD).

What do computational predictors say about AOX1 p.Lys515Arg (c.1544A>G)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

AOX1 p.Lys515Arg

c.1544A>G · VCV4641395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -1.40	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 1.3	GERP -3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 85 kb · p 0.85 · regional, not allelic
Overall
CADD	13.14	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 0.0205% Middle Eastern · 1/4,880 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000616% 9/1,460,388 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0205%	4,880
African / African-American	0.008%	12,500
Remaining individualsnot grpmax-eligible	0.00321%	31,190

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: AOX1
Protein: p.Lys515Arg
Coding: c.1544A>G
MANE Select: NM_001159
Type: single nucleotide variant
Location: chr2:200613899 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 8 PDB
Residue 515: an α-helix

Full AOX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOX1 p.Lys515Glu Uncertain significance ★ ⚠ same residue
AOX1 p.Ala1083Gly Benign ★★ same type
AOX1 p.Arg130= Benign ★★ same type
AOX1 p.Gln314Arg Benign ★★ same type
AOX1 p.Gln737= Benign ★★ same type
AOX1 p.Ile598Asn Benign ★★ ⚠ same type
AOX1 p.Leu553= Benign ★★ same type
AOX1 p.Pro1245= Benign ★★ same type

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/aox1-p-lys515arg (accessed [today's date]).

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