Is AOC3 p.Arg601Gln (c.1802G>A) pathogenic?

AOC3 p.Arg601Gln (c.1802G>A) is classified Uncertain significance in AOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.11); Ultra-rare (popmax 0.0275%, afr).

How common is AOC3 p.Arg601Gln (c.1802G>A) in the general population?

AOC3 p.Arg601Gln (c.1802G>A) is ultra-rare (popmax 0.0275%, afr) (gnomAD).

What do computational predictors say about AOC3 p.Arg601Gln (c.1802G>A)?

AlphaMissense predicts likely benign (score 0.11) — an in-silico prediction, not a clinical call.

AOC3 p.Arg601Gln

c.1802G>A · rs138325720 · VCV2265980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.11 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.11	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -10.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	25.2	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 0.0275% African / African-American · 20/72,804 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0152%

Overall 0.002% 31/1,552,672 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0275%	3,640
Finnishnot grpmax-eligible	0.00808%	12,369
South Asian	0.00358%	27,923
Admixed American	0.00186%	53,656
Remaining individualsnot grpmax-eligible	0.00167%	59,730
European (non-Finnish)	8.73e-05%	1,144,998

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.Arg601Gln
Coding: c.1802G>A
MANE Select: NM_003734
dbSNP: rs138325720
Type: single nucleotide variant
Location: chr17:42854649 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB
Residue 601: 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.Arg329Gln Benign/Likely 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

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-arg601gln (accessed [today's date]).

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