Is AOC3 p.Phe184Cys (c.551T>G) pathogenic?

AOC3 p.Phe184Cys (c.551T>G) is classified Uncertain significance in AOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely benign (0.2684); Very rare (popmax 0.00534%, afr).

How common is AOC3 p.Phe184Cys (c.551T>G) in the general population?

AOC3 p.Phe184Cys (c.551T>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about AOC3 p.Phe184Cys (c.551T>G)?

AlphaMissense predicts likely benign (score 0.2684) — an in-silico prediction, not a clinical call.

AOC3 p.Phe184Cys

c.551T>G · VCV3921615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2684 · 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	0.2684	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -9.41	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 0.16	GERP 0.91, phastCons 0.001
Regional constraint	o/e 0.86	unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	22.1	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 · 4/74,912 alleles

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

Overall 0.00031% 5/1,613,540 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,728
European (non-Finnish)	8.47e-05%	1,180,016

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.Phe184Cys
Coding: c.551T>G
MANE Select: NM_003734
Type: single nucleotide variant
Location: chr17:42851894 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB
Residue 184: an α-helix

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-phe184cys (accessed [today's date]).

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