Is CPEB1 p.Phe3Ser (c.8T>C) pathogenic?

CPEB1 p.Phe3Ser (c.8T>C) is classified Uncertain significance in CPEB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). Ultra-rare (popmax 0.0289%, nfe).

How common is CPEB1 p.Phe3Ser (c.8T>C) in the general population?

CPEB1 p.Phe3Ser (c.8T>C) is ultra-rare (popmax 0.0289%, nfe) (gnomAD).

CPEB1 p.Phe3Ser

c.8T>C · rs892292072 · VCV2354792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0289%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.34, phastCons 1
Overall
CADD	16.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0289% European (non-Finnish) · 292/1,009,664 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0251%

Overall 0.0234% 297/1,269,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0289%	3,458
Remaining individualsnot grpmax-eligible	0.00857%	11,672
African / African-American	0.00156%	64,238

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: CPEB1
Protein: p.Phe3Ser
Coding: c.8T>C
MANE Select: NM_001365242 · reported on NM_030594
dbSNP: rs892292072
Type: single nucleotide variant
Location: chr15:82647863 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.05 · 5 PDB

Full CPEB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB1 p.Ala109Val Uncertain significance ★ same type
CPEB1 p.Ala147Asp Uncertain significance ★ same type
CPEB1 p.Arg136Gly Uncertain significance ★ same type
CPEB1 p.Arg196Cys Uncertain significance ★ same type
CPEB1 p.Arg200Gln Uncertain significance ★ same type
CPEB1 p.Arg200Trp Uncertain significance ★ same type
CPEB1 p.Arg233His Uncertain significance ★ same type
CPEB1 p.Arg452Lys 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/cpeb1-p-phe3ser (accessed [today's date]).

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