Is AOC3 p.Val14Ile (c.40G>A) pathogenic?

AOC3 p.Val14Ile (c.40G>A) is classified Uncertain significance in AOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0331%, mid).

How common is AOC3 p.Val14Ile (c.40G>A) in the general population?

AOC3 p.Val14Ile (c.40G>A) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about AOC3 p.Val14Ile (c.40G>A)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

AOC3 p.Val14Ile

c.40G>A · rs150796667 · VCV2470727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.88	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 0.54	GERP -1.2, phastCons 0.005
Regional constraint	o/e 0.86	unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	14.03	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 0.0331% Middle Eastern · 2/6,044 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00341% 55/1,611,444 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,022
Remaining individualsnot grpmax-eligible	0.00962%	10,392
East Asian	0.00669%	14,950
European (non-Finnish)	0.00365%	27,408
African / African-American	0.00133%	74,994

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.Val14Ile
Coding: c.40G>A
MANE Select: NM_003734
dbSNP: rs150796667
Type: single nucleotide variant
Location: chr17:42851383 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB

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-val14ile (accessed [today's date]).

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