Is CPEB2 p.Gln416Pro (c.1247A>C) pathogenic?

CPEB2 p.Gln416Pro (c.1247A>C) is classified Uncertain significance in CPEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Very rare (popmax 0.000123%, nfe).

How common is CPEB2 p.Gln416Pro (c.1247A>C) in the general population?

CPEB2 p.Gln416Pro (c.1247A>C) is very rare (popmax 0.000123%, nfe) (gnomAD).

CPEB2 p.Gln416Pro

c.1247A>C · rs1722394237 · VCV3076625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000123%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.041	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.31	GERP 0.36, phastCons 0.026
Regional constraint	o/e 1.34	unconstrained · MANE · 50 kb · p 8.8e-28 · regional, not allelic
Overall
CADD	9.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000123% European (non-Finnish) · 1/812,718 alleles

Overall 0.000111% 1/903,046 alleles · very rare

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: CPEB2
Protein: p.Gln416Pro
Coding: c.1247A>C
MANE Select: NM_001177382
dbSNP: rs1722394237
Type: single nucleotide variant
Location: chr4:15003920 (GRCh38)
Gene constraint: LOEUF 1.328 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.86
Residue 416: the rrm 1 domain

Full CPEB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB2 p.Gln416His Uncertain significance ★ same residue
CPEB2 p.Ala113Val Uncertain significance ★ same type
CPEB2 p.Ala27Val Uncertain significance ★ same type
CPEB2 p.Ala287Ser Uncertain significance ★ same type
CPEB2 p.Ala288Val Uncertain significance ★ same type
CPEB2 p.Ala494Ser Uncertain significance ★ same type
CPEB2 p.Ala517Thr Uncertain significance ★ same type
CPEB2 p.Ala540Val 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/cpeb2-p-gln416pro (accessed [today's date]).

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