Is AOC3 p.Arg329Gln (c.986G>A) pathogenic?

AOC3 p.Arg329Gln (c.986G>A) is classified Benign/Likely benign in AOC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-01). AlphaMissense: likely benign (0.0594); Rare (popmax 0.938%, nfe).

How common is AOC3 p.Arg329Gln (c.986G>A) in the general population?

AOC3 p.Arg329Gln (c.986G>A) is rare (popmax 0.938%, nfe) (gnomAD).

What do computational predictors say about AOC3 p.Arg329Gln (c.986G>A)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

AOC3 p.Arg329Gln

c.986G>A · rs2229595 · VCV717753

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.938%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.63	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 -10	GERP -4.1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	5.496	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 0.938% European (non-Finnish) · 11,073/1,180,014 alleles

Filtering AF 0.924% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.918%

Overall 0.791% 12,772/1,614,120 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.2%	83
European (non-Finnish)grpmax	0.938%	107
Finnishnot grpmax-eligible	0.715%	140
Remaining individualsnot grpmax-eligible	0.61%	164
Admixed American	0.52%	192
African / African-American	0.168%	595
Middle Eastern	0.132%	757
South Asian	0.0648%	1,544

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AOC3
Protein: p.Arg329Gln
Coding: c.986G>A
MANE Select: NM_003734
dbSNP: rs2229595
Type: single nucleotide variant
Location: chr17:42852329 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB
Residue 329: a UniProt-annotated variant site (in); a β-strand

Full AOC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOC3 p.Arg73Cys Uncertain significance ★★ ⚠ same type
AOC3 p.Ala582Thr Benign ★★ same type
AOC3 p.Arg441Trp Benign ★★ ⚠ same type
AOC3 p.Arg566Gln Likely benign ★★ same type
AOC3 p.Ile371Thr Benign ★★ same type
AOC3 p.Tyr271= Likely benign ★★ same type
AOC3 p.Tyr406Asn Benign ★★ ⚠ same type
AOC3 p.Ala124Thr 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/aoc3-p-arg329gln (accessed [today's date]).

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