Is AOC2 p.Arg69Cys (c.205C>T) pathogenic?

AOC2 p.Arg69Cys (c.205C>T) is classified Uncertain significance in AOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1054); Ultra-rare (popmax 0.0549%, nfe).

How common is AOC2 p.Arg69Cys (c.205C>T) in the general population?

AOC2 p.Arg69Cys (c.205C>T) is ultra-rare (popmax 0.0549%, nfe) (gnomAD).

What do computational predictors say about AOC2 p.Arg69Cys (c.205C>T)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

AOC2 p.Arg69Cys

c.205C>T · rs150378203 · VCV2353741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -10.07	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 1.3	GERP -4.1, phastCons 0.18
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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0549% European (non-Finnish) · 647/1,179,108 alleles

Filtering AF 0.0513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.0494% 796/1,612,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0875%	1,143
Remaining individualsnot grpmax-eligible	0.0657%	1,522
European (non-Finnish)grpmax	0.0549%	1,822
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,957
Middle Eastern	0.033%	3,028
Admixed American	0.0217%	4,614
South Asian	0.0187%	5,355
East Asian	0.00892%	11,209
African / African-American	0.008%	12,503

Finnish 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: AOC2
Protein: p.Arg69Cys
Coding: c.205C>T
MANE Select: NM_009590
dbSNP: rs150378203
Type: single nucleotide variant
Location: chr17:42844831 (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.Arg69His Uncertain significance ★ ⚠ same residue
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

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-arg69cys (accessed [today's date]).

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