Is ADCY1 p.Asp366= (c.1098C>T) pathogenic?

ADCY1 p.Asp366= (c.1098C>T) is classified Likely benign in ADCY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-13). Ultra-rare (popmax 0.0467%, amr).

How common is ADCY1 p.Asp366= (c.1098C>T) in the general population?

ADCY1 p.Asp366= (c.1098C>T) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

ADCY1 p.Asp366=

c.1098C>T · rs151091562 · VCV2712281

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

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 1.6	GERP 1.8, phastCons 1
Overall
CADD	11.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0467% Admixed American · 28/60,008 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00173% 28/1,614,088 alleles · ultra-rare

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: ADCY1
Protein: p.Asp366=
Coding: c.1098C>T
MANE Select: NM_021116
dbSNP: rs151091562
Type: single nucleotide variant
Location: chr7:45648747 (GRCh38)
Gene constraint: LOEUF 0.346 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.34

Full ADCY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCY1 p.Ala698Thr Uncertain significance ★★ ⚠ same type
ADCY1 p.Arg147Pro Uncertain significance ★★ ⚠ same type
ADCY1 p.Arg30Pro Uncertain significance ★★ ⚠ same type
ADCY1 p.Arg34Gly Uncertain significance ★★ ⚠ same type
ADCY1 p.Arg412Ser Uncertain significance ★★ ⚠ same type
ADCY1 p.Arg597Gln Uncertain significance ★★ ⚠ same type
ADCY1 p.Glu596Lys Uncertain significance ★★ ⚠ same type
ADCY1 p.Gly73Ser Uncertain significance ★★ ⚠ 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/adcy1-p-asp366 (accessed [today's date]).

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