Is CPNE2 p.Val40Ala (c.119T>C) pathogenic?

CPNE2 p.Val40Ala (c.119T>C) is classified Uncertain significance in CPNE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely pathogenic (0.6705); Absent from gnomAD v4.1.

How common is CPNE2 p.Val40Ala (c.119T>C) in the general population?

CPNE2 p.Val40Ala (c.119T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPNE2 p.Val40Ala (c.119T>C)?

AlphaMissense predicts likely pathogenic (score 0.6705) — an in-silico prediction, not a clinical call.

CPNE2 p.Val40Ala

c.119T>C · rs2545440750 · VCV3076753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6705 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6705	likely pathogenic
REVEL	0.136	moderately benign-leaning
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,579 bp · p 0.91 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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: CPNE2
Protein: p.Val40Ala
Coding: c.119T>C
MANE Select: NM_152727
dbSNP: rs2545440750
Type: single nucleotide variant
Location: chr16:57110861 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.76
Residue 40: the c2 1 domain

Full CPNE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPNE2 p.Ala12Val Uncertain significance ★ ⚠ same type
CPNE2 p.Ala147Thr Uncertain significance ★ ⚠ same type
CPNE2 p.Ala14Glu Uncertain significance ★ ⚠ same type
CPNE2 p.Ala378Val Uncertain significance ★ ⚠ same type
CPNE2 p.Ala475Gly Uncertain significance ★ ⚠ same type
CPNE2 p.Ala475Val Uncertain significance ★ ⚠ same type
CPNE2 p.Ala478Thr Uncertain significance ★ ⚠ same type
CPNE2 p.Ala548Thr 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/cpne2-p-val40ala (accessed [today's date]).

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