Is ADCY9 p.Pro366Arg (c.1097C>G) pathogenic?

ADCY9 p.Pro366Arg (c.1097C>G) is classified Uncertain significance in ADCY9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: ambiguous (0.4829); Absent from gnomAD v4.1.

How common is ADCY9 p.Pro366Arg (c.1097C>G) in the general population?

ADCY9 p.Pro366Arg (c.1097C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADCY9 p.Pro366Arg (c.1097C>G)?

AlphaMissense predicts ambiguous (score 0.4829) — an in-silico prediction, not a clinical call.

ADCY9 p.Pro366Arg

c.1097C>G · rs1159195754 · VCV2552295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4829 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4829	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -5.46	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 684 bp · p 2.5e-05 · regional, not allelic
Overall
CADD	26.2	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: ADCY9
Protein: p.Pro366Arg
Coding: c.1097C>G
MANE Select: NM_001116
dbSNP: rs1159195754
Type: single nucleotide variant
Location: chr16:4114346 (GRCh38)
Gene constraint: LOEUF 0.603 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.00 · 6 PDB
Residue 366: the 'disordered' region

Full ADCY9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCY9 c.2828+4C>G Likely benign ★★ same type
ADCY9 p.Ala905= Benign ★★ same type
ADCY9 p.Arg998= Benign/Likely benign ★★ same type
ADCY9 p.Ile1110= Benign ★★ same type
ADCY9 p.Leu878= Benign ★★ same type
ADCY9 p.Lys564Gln Likely benign ★★ same type
ADCY9 p.Phe1161= Benign ★★ same type
ADCY9 p.Ser661Gly 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/adcy9-p-pro366arg (accessed [today's date]).

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