Is CNPY3 p.Ala8Pro (c.22G>C) pathogenic?

CNPY3 p.Ala8Pro (c.22G>C) is classified Uncertain significance in CNPY3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0782); Absent from gnomAD v4.1.

How common is CNPY3 p.Ala8Pro (c.22G>C) in the general population?

CNPY3 p.Ala8Pro (c.22G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNPY3 p.Ala8Pro (c.22G>C)?

AlphaMissense predicts likely benign (score 0.0782) — an in-silico prediction, not a clinical call.

CNPY3 p.Ala8Pro

c.22G>C · rs534665673 · VCV3146655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0782	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.97	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 5	GERP -0.78, phastCons 0.98
Regional constraint	o/e 1.41	unconstrained · MANE · 150 bp · p 0.0013 · regional, not allelic
Overall
CADD	22.6	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

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: CNPY3
Protein: p.Ala8Pro
Coding: c.22G>C
MANE Select: NM_006586
dbSNP: rs534665673
Type: single nucleotide variant
Location: chr6:42929592 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.76

Full CNPY3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNPY3 p.Glu154Lys Uncertain significance ★★ ⚠ same type
CNPY3 p.Glu98Lys Uncertain significance ★★ ⚠ same type
CNPY3 p.Gly67Ser Uncertain significance ★★ ⚠ same type
CNPY3 p.Lys105Met Uncertain significance ★★ ⚠ same type
CNPY3 p.Ser231Cys Uncertain significance ★★ ⚠ same type
CNPY3 p.Tyr149Cys Uncertain significance ★★ ⚠ same type
CNPY3 p.Cys194= Likely benign ★★ same type
CNPY3 p.Gly237= Likely 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/cnpy3-p-ala8pro (accessed [today's date]).

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