Is CPEB1 p.Pro4Ser (c.10C>T) pathogenic?

CPEB1 p.Pro4Ser (c.10C>T) is classified Uncertain significance in CPEB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). Rare (popmax 0.15%, nfe).

How common is CPEB1 p.Pro4Ser (c.10C>T) in the general population?

CPEB1 p.Pro4Ser (c.10C>T) is rare (popmax 0.15%, nfe) (gnomAD).

CPEB1 p.Pro4Ser

c.10C>T · rs372164501 · VCV2348704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.15%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.75, phastCons 1
Overall
CADD	17.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% European (non-Finnish) · 1,511/1,010,002 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.147% 1,868/1,270,462 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.21%	83
Remaining individualsnot grpmax-eligible	0.222%	450
European (non-Finnish)grpmax	0.15%	668
Middle Eastern	0.0534%	1,872
African / African-American	0.0295%	3,391
Admixed American	0.0251%	3,986
South Asian	0.0136%	7,376
Finnishnot grpmax-eligible	0.00293%	34,088

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: CPEB1
Protein: p.Pro4Ser
Coding: c.10C>T
MANE Select: NM_001365242 · reported on NM_030594
dbSNP: rs372164501
Type: single nucleotide variant
Location: chr15:82647861 (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-pro4ser (accessed [today's date]).

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