Is CNPY4 p.Pro3Ser (c.7C>T) pathogenic?

CNPY4 p.Pro3Ser (c.7C>T) is classified Uncertain significance in CNPY4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely benign (0.0884); Rare (popmax 0.109%, afr).

How common is CNPY4 p.Pro3Ser (c.7C>T) in the general population?

CNPY4 p.Pro3Ser (c.7C>T) is rare (popmax 0.109%, afr) (gnomAD).

What do computational predictors say about CNPY4 p.Pro3Ser (c.7C>T)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

CNPY4 p.Pro3Ser

c.7C>T · VCV3494545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.38	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 2	GERP 2.1, phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 5,140 bp · p 0.22 · regional, not allelic
Overall
CADD	19.11	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

Grpmax group 0.109% African / African-American · 82/75,054 alleles

Filtering AF 0.0902% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0831%

Overall 0.0052% 84/1,614,184 alleles · rare exomes 36/1,461,828 · genomes 48/152,356 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.109%	915
Admixed American	0.00333%	30,003

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: CNPY4
Protein: p.Pro3Ser
Coding: c.7C>T
MANE Select: NM_152755
Type: single nucleotide variant
Location: chr7:100119751 (GRCh38)
Gene constraint: LOEUF 1.33 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.97

Full CNPY4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNPY4 p.Ala104Thr Uncertain significance ★ ⚠ same type
CNPY4 p.Ala21Thr Uncertain significance ★ ⚠ same type
CNPY4 p.Ala21Val Uncertain significance ★ ⚠ same type
CNPY4 p.Arg106His Uncertain significance ★ ⚠ same type
CNPY4 p.Arg245Gln Uncertain significance ★ ⚠ same type
CNPY4 p.Arg54Cys Uncertain significance ★ ⚠ same type
CNPY4 p.Arg57Gln Uncertain significance ★ ⚠ same type
CNPY4 p.Arg96Gln 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/cnpy4-p-pro3ser (accessed [today's date]).

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