AOC3 p.Cys748Arg
c.2242T>C · VCV3402962
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6748 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6748 | likely pathogenic |
|---|---|---|
| REVEL | 0.325 | indeterminate |
| SaProt | LLR -5.38 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic |
| Overall | ||
| CADD | 27.7 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AOC3
- Protein
- p.Cys748Arg
- Coding
- c.2242T>C
- MANE Select
- NM_003734
- Type
- single nucleotide variant
- Location
- chr17:42856500 (GRCh38)
- Gene constraint
- LOEUF 1.056 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.15 · 11 PDB
- Residue 748
- a disulfide bond
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-cys748arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown