Is CPEB2 p.Ile741Val (c.2221A>G) pathogenic?

CPEB2 p.Ile741Val (c.2221A>G) is classified Uncertain significance in CPEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). Very rare (popmax 0.00415%, afr).

How common is CPEB2 p.Ile741Val (c.2221A>G) in the general population?

CPEB2 p.Ile741Val (c.2221A>G) is very rare (popmax 0.00415%, afr) (gnomAD).

CPEB2 p.Ile741Val

c.2221A>G · VCV3496340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00415%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.3	GERP -1.3, phastCons 1
Regional constraint	o/e 1.34	unconstrained · MANE · 50 kb · p 8.8e-28 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% African / African-American · 3/72,280 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000506%

Overall 0.000522% 8/1,533,542 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00415%	24,093
Admixed American	0.00187%	53,448
Remaining individualsnot grpmax-eligible	0.00172%	58,244
European (non-Finnish)	0.000265%	377,769

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.Ile741Val
Coding: c.2221A>G
Type: single nucleotide variant
Location: chr4:15052434 (GRCh38)

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

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-ile741val (accessed [today's date]).

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