Is ACOX2 p.Asn68Ser (c.203A>G) pathogenic?

ACOX2 p.Asn68Ser (c.203A>G) is classified Uncertain significance in ACOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.0867); Very rare (popmax 0.00534%, afr).

How common is ACOX2 p.Asn68Ser (c.203A>G) in the general population?

ACOX2 p.Asn68Ser (c.203A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ACOX2 p.Asn68Ser (c.203A>G)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

ACOX2 p.Asn68Ser

c.203A>G · rs1005112132 · VCV2459286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -4.90	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 -1.5	GERP -4.4
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.14 · regional, not allelic
Overall
CADD	0.649	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 0.00534% African / African-American · 4/74,896 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,018 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: ACOX2
Protein: p.Asn68Ser
Coding: c.203A>G
MANE Select: NM_003500
dbSNP: rs1005112132
Type: single nucleotide variant
Location: chr3:58534480 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.49

Full ACOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOX2 p.Ala106Val Uncertain significance ★★ ⚠ same type
ACOX2 p.Ala48Glu Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg197Gln Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg197Trp Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg215Trp Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg318His Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg323Cys Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg323His Uncertain significance ★★ ⚠ 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/acox2-p-asn68ser (accessed [today's date]).

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