Is CPEB3 p.Val280= (c.840C>T) pathogenic?

CPEB3 p.Val280= (c.840C>T) is classified Benign in CPEB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-24). Common (popmax 5.7%, afr) — too common for a highly-penetrant pathogenic allele.

CPEB3 p.Val280=

Q: How common is CPEB3 p.Val280= (c.840C>T) in the general population?

CPEB3 p.Val280= (c.840C>T) is common (popmax 5.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.840C>T · rs115735799 · VCV785323

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.7%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.4
Overall
CADD	5.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.7% African / African-American · 4,248/74,524 alleles

Filtering AF 5.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5%

Overall 0.302% 4,756/1,574,952 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.7%	18
Remaining individualsnot grpmax-eligible	0.348%	288
Admixed American	0.296%	338
Middle Eastern	0.24%	417
South Asian	0.0196%	5,094
European (non-Finnish)	0.00923%	10,837

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: CPEB3
Protein: p.Val280=
Coding: c.840C>T
MANE Select: NM_014912
dbSNP: rs115735799
Type: single nucleotide variant
Location: chr10:92239511 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 58.59 · 6 PDB

Full CPEB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB3 p.Ala101Ser Uncertain significance ★ ⚠ same type
CPEB3 p.Ala118Thr Uncertain significance ★ ⚠ same type
CPEB3 p.Ala254Pro Uncertain significance ★ ⚠ same type
CPEB3 p.Ala388Thr Uncertain significance ★ ⚠ same type
CPEB3 p.Ala409Gly Uncertain significance ★ ⚠ same type
CPEB3 p.Ala61Val Uncertain significance ★ ⚠ same type
CPEB3 p.Ala64Thr Uncertain significance ★ ⚠ same type
CPEB3 p.Ala668Ser 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/cpeb3-p-val280 (accessed [today's date]).

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