Is CPEB2 p.Gly367Glu (c.1100G>A) pathogenic?

CPEB2 p.Gly367Glu (c.1100G>A) is classified Uncertain significance in CPEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Very rare (popmax 0.000106%, nfe).

How common is CPEB2 p.Gly367Glu (c.1100G>A) in the general population?

CPEB2 p.Gly367Glu (c.1100G>A) is very rare (popmax 0.000106%, nfe) (gnomAD).

CPEB2 p.Gly367Glu

c.1100G>A · rs1200953566 · VCV2313616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000106%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.277	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.43, phastCons 1
Regional constraint	o/e 1.34	unconstrained · MANE · 50 kb · p 8.8e-28 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000106% European (non-Finnish) · 1/942,928 alleles

Overall 0.000426% 5/1,172,892 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0124%	8,067
Remaining individualsnot grpmax-eligible	0.00468%	21,366
European (non-Finnish)grpmax	0.000106%	942,925

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly367Glu
Coding: c.1100G>A
MANE Select: NM_001177382
dbSNP: rs1200953566
Type: single nucleotide variant
Location: chr4:15003773 (GRCh38)
Gene constraint: LOEUF 1.328 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.86
Residue 367: the rrm 1 domain

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

Similar variants

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
CPEB2 p.Ala541Thr 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-gly367glu (accessed [today's date]).

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