Is ADCY3 p.Ser511= (c.1533G>A) pathogenic?

ADCY3 p.Ser511= (c.1533G>A) is classified Uncertain significance in ADCY3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-03). Ultra-rare (popmax 0.0317%, amr); Associated with ADCY3-related disorder.

What condition is associated with ADCY3 p.Ser511= (c.1533G>A)?

ADCY3 p.Ser511= (c.1533G>A) is associated with ADCY3-related disorder (ClinVar).

How common is ADCY3 p.Ser511= (c.1533G>A) in the general population?

ADCY3 p.Ser511= (c.1533G>A) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

ADCY3 p.Ser511=

c.1533G>A · rs771095823 · VCV3034110

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Conditions

ADCY3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.15	GERP 2.3, phastCons 0.41
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% Admixed American · 19/59,932 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00323% 52/1,611,398 alleles · ultra-rare exomes 51/1,459,602 · genomes 1/151,796 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,154
South Asian	0.0297%	3,368
Middle Eastern	0.0209%	4,790
East Asian	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,306
African / African-American	0.00134%	74,734
European (non-Finnish)	0.00017%	589,859

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: ADCY3
Protein: p.Ser511=
Coding: c.1533G>A
MANE Select: NM_004036
dbSNP: rs771095823
Type: single nucleotide variant
Location: chr2:24838445 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.86
Residue 511: the 'disordered' region

Full ADCY3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ADCY3-related disorder

Similar variants

ADCY3 p.Ser511Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ADCY3 p.Val195Met Uncertain significance ★★ ⚠ same condition
ADCY3 c.2496-13C>T Uncertain significance ★ same condition
ADCY3 p.Arg252Cys Uncertain significance ★ ⚠ same condition
ADCY3 p.Arg564His Uncertain significance ★ ⚠ same condition
ADCY3 p.Arg623Cys Uncertain significance ★ ⚠ same condition
ADCY3 p.Glu346Lys Uncertain significance ★ ⚠ same condition
ADCY3 p.Met461Ile Uncertain significance ★ ⚠ same condition

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/adcy3-p-ser511 (accessed [today's date]).

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