Is CPEB4 p.Arg350Cys (c.1048C>T) pathogenic?

CPEB4 p.Arg350Cys (c.1048C>T) is classified Uncertain significance in CPEB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.6393); Very rare (popmax 0.000424%, nfe).

How common is CPEB4 p.Arg350Cys (c.1048C>T) in the general population?

CPEB4 p.Arg350Cys (c.1048C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CPEB4 p.Arg350Cys (c.1048C>T)?

AlphaMissense predicts likely pathogenic (score 0.6393) — an in-silico prediction, not a clinical call.

CPEB4 p.Arg350Cys

c.1048C>T · VCV4656104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6393 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6393	likely pathogenic
REVEL	0.342	indeterminate
SaProt	LLR -10.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 55 kb · p 0.00011 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000424% European (non-Finnish) · 5/1,180,038 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,064 alleles · very rare

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.Arg350Cys
Coding: c.1048C>T
MANE Select: NM_030627
Type: single nucleotide variant
Location: chr5:173890781 (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.Arg444Cys 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-arg350cys (accessed [today's date]).

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