Is AOC3 p.His203Arg (c.608A>G) pathogenic?

AOC3 p.His203Arg (c.608A>G) is classified Likely benign in AOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-09). AlphaMissense: likely benign (0.0538); Ultra-rare (popmax 0.0362%, sas).

How common is AOC3 p.His203Arg (c.608A>G) in the general population?

AOC3 p.His203Arg (c.608A>G) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

What do computational predictors say about AOC3 p.His203Arg (c.608A>G)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

AOC3 p.His203Arg

c.608A>G · rs630079 · VCV2323644

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -3.69	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 -13	GERP -4
Regional constraint	o/e 0.86	unconstrained · MANE · 5,203 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	0.001	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

Grpmax group 0.0362% South Asian · 33/91,074 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.0088% 142/1,613,716 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Middle Eastern	0.0165%	6,054
African / African-American	0.0133%	7,504
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
Admixed American	0.01%	10,001
East Asian	0.00892%	11,216
European (non-Finnish)	0.00653%	15,323

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.His203Arg
Coding: c.608A>G
MANE Select: NM_003734
dbSNP: rs630079
Type: single nucleotide variant
Location: chr17:42851951 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 11 PDB
Residue 203: a UniProt-annotated variant site (in); a turn

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-his203arg (accessed [today's date]).

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