Is AOC3 p.Ala575= (c.1725C>T) pathogenic?

AOC3 p.Ala575= (c.1725C>T) is classified Benign in AOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-11). Ultra-rare (popmax 0.066%, nfe).

How common is AOC3 p.Ala575= (c.1725C>T) in the general population?

AOC3 p.Ala575= (c.1725C>T) is ultra-rare (popmax 0.066%, nfe) (gnomAD).

AOC3 p.Ala575=

c.1725C>T · rs146596949 · VCV729247

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.2
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% European (non-Finnish) · 778/1,178,256 alleles

Filtering AF 0.0622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0606%

Overall 0.0614% 989/1,610,366 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.383%	261
Remaining individualsnot grpmax-eligible	0.085%	1,176
European (non-Finnish)grpmax	0.066%	1,514
Admixed American	0.0519%	1,927
Middle Eastern	0.0165%	6,044
African / African-American	0.00935%	10,698
Finnishnot grpmax-eligible	0.00472%	21,176
East Asian	0.00224%	44,614
South Asian	0.00221%	45,270

Ashkenazi Jewish 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: AOC3
Protein: p.Ala575=
Coding: c.1725C>T
MANE Select: NM_003734
dbSNP: rs146596949
Type: single nucleotide variant
Location: chr17:42854572 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB
Residue 575: 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-ala575 (accessed [today's date]).

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