Is AOC3 p.Met380Val (c.1138A>G) pathogenic?

AOC3 p.Met380Val (c.1138A>G) is classified Uncertain significance in AOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.0961); Very rare (popmax 0.00169%, nfe).

How common is AOC3 p.Met380Val (c.1138A>G) in the general population?

AOC3 p.Met380Val (c.1138A>G) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about AOC3 p.Met380Val (c.1138A>G)?

AlphaMissense predicts likely benign (score 0.0961) — an in-silico prediction, not a clinical call.

AOC3 p.Met380Val

c.1138A>G · rs749777027 · VCV2517580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0961	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.69	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 -0.58	GERP -1.5
Regional constraint	o/e 0.86	unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	11.7	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 0.00169% European (non-Finnish) · 20/1,180,048 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00136% 22/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00169%	59,002
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,930

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.Met380Val
Coding: c.1138A>G
MANE Select: NM_003734
dbSNP: rs749777027
Type: single nucleotide variant
Location: chr17:42852481 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB
Residue 380: 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-met380val (accessed [today's date]).

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