Is AOC2 p.Arg347Gln (c.1040G>A) pathogenic?

AOC2 p.Arg347Gln (c.1040G>A) is classified Uncertain significance in AOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely benign (0.0864); Very rare (popmax 0.00668%, eas).

How common is AOC2 p.Arg347Gln (c.1040G>A) in the general population?

AOC2 p.Arg347Gln (c.1040G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about AOC2 p.Arg347Gln (c.1040G>A)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

AOC2 p.Arg347Gln

c.1040G>A · rs1374026963 · VCV2411722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -9.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP -0.22, phastCons 0.8
Regional constraint	o/e 1.05	unconstrained · MANE · 5,718 bp · p 0.1 · regional, not allelic
Overall
CADD	22.7	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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
African / African-American	0.00267%	37,456
European (non-Finnish)	8.47e-05%	1,180,045

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: AOC2
Protein: p.Arg347Gln
Coding: c.1040G>A
MANE Select: NM_009590
dbSNP: rs1374026963
Type: single nucleotide variant
Location: chr17:42845666 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.10

Full AOC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOC2 p.Arg597= Benign ★★ same type
AOC2 p.Pro141Leu Benign ★★ ⚠ same type
AOC2 p.Ala104Thr Uncertain significance ★ ⚠ same type
AOC2 p.Ala218Thr Uncertain significance ★ ⚠ same type
AOC2 p.Ala415Pro Uncertain significance ★ ⚠ same type
AOC2 p.Ala450Val Uncertain significance ★ ⚠ same type
AOC2 p.Ala519Gly Uncertain significance ★ ⚠ same type
AOC2 p.Ala592Thr 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/aoc2-p-arg347gln (accessed [today's date]).

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