Is ADCYAP1 p.Pro77Ser (c.229C>T) pathogenic?

ADCYAP1 p.Pro77Ser (c.229C>T) is classified Uncertain significance in ADCYAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0936); No allele count reported in gnomAD v4.1 (AN 1,448,274).

How common is ADCYAP1 p.Pro77Ser (c.229C>T) in the general population?

ADCYAP1 p.Pro77Ser (c.229C>T) is no allele count reported in gnomAD v4.1 (AN 1,448,274) (gnomAD).

What do computational predictors say about ADCYAP1 p.Pro77Ser (c.229C>T)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

ADCYAP1 p.Pro77Ser

c.229C>T · VCV4831802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,448,274)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 2.2, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 4,245 bp · p 0.00015 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,448,274). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADCYAP1
Protein: p.Pro77Ser
Coding: c.229C>T
MANE Select: NM_001099733
Type: single nucleotide variant
Location: chr18:907777 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 63.64 · 13 PDB

Full ADCYAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCYAP1 p.Ala29Val Uncertain significance ★ ⚠ same type
ADCYAP1 p.Ala61Ser Uncertain significance ★ ⚠ same type
ADCYAP1 p.Ala73Val Uncertain significance ★ ⚠ same type
ADCYAP1 p.Arg145Gly Uncertain significance ★ ⚠ same type
ADCYAP1 p.Arg172Gly Uncertain significance ★ ⚠ same type
ADCYAP1 p.Arg81Gly Uncertain significance ★ ⚠ same type
ADCYAP1 p.Arg93Cys Uncertain significance ★ ⚠ same type
ADCYAP1 p.Arg93Leu 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/adcyap1-p-pro77ser (accessed [today's date]).

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