Is CPEB4 p.Pro157His (c.470C>A) pathogenic?

CPEB4 p.Pro157His (c.470C>A) is classified Uncertain significance in CPEB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.1164); Rare (popmax 0.101%, nfe).

How common is CPEB4 p.Pro157His (c.470C>A) in the general population?

CPEB4 p.Pro157His (c.470C>A) is rare (popmax 0.101%, nfe) (gnomAD).

What do computational predictors say about CPEB4 p.Pro157His (c.470C>A)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

CPEB4 p.Pro157His

c.470C>A · rs149568017 · VCV2410230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 55 kb · p 0.00011 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% European (non-Finnish) · 1,193/1,180,032 alleles

Filtering AF 0.0963% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0943%

Overall 0.0785% 1,267/1,614,054 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.101%	989
Remaining individualsnot grpmax-eligible	0.0736%	1,358
African / African-American	0.0173%	5,764
Admixed American	0.01%	10,001
Finnishnot grpmax-eligible	0.00625%	16,001
South Asian	0.00439%	22,772
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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: CPEB4
Protein: p.Pro157His
Coding: c.470C>A
MANE Select: NM_030627
dbSNP: rs149568017
Type: single nucleotide variant
Location: chr5:173890203 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.58 · 3 PDB

Full CPEB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB4 p.Ala104Ser Uncertain significance ★ ⚠ same type
CPEB4 p.Ala197Pro Uncertain significance ★ ⚠ same type
CPEB4 p.Ala349Ser Uncertain significance ★ ⚠ same type
CPEB4 p.Ala610Thr Uncertain significance ★ ⚠ same type
CPEB4 p.Ala80Thr Uncertain significance ★ ⚠ same type
CPEB4 p.Arg134Lys Uncertain significance ★ ⚠ same type
CPEB4 p.Arg319Lys Uncertain significance ★ ⚠ same type
CPEB4 p.Arg350Cys 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/cpeb4-p-pro157his (accessed [today's date]).

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