Is CPEB4 p.Arg493His (c.1478G>A) pathogenic?

CPEB4 p.Arg493His (c.1478G>A) is classified Uncertain significance in CPEB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). AlphaMissense: ambiguous (0.4287); Very rare (popmax 0.00223%, eas).

How common is CPEB4 p.Arg493His (c.1478G>A) in the general population?

CPEB4 p.Arg493His (c.1478G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CPEB4 p.Arg493His (c.1478G>A)?

AlphaMissense predicts ambiguous (score 0.4287) — an in-silico prediction, not a clinical call.

CPEB4 p.Arg493His

c.1478G>A · rs1313241047 · VCV2312882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4287	ambiguous
REVEL	0.437	indeterminate
SaProt	LLR -13.37	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 4,896 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,826 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,460,824 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,826
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.000254%	393,097

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.Arg493His
Coding: c.1478G>A
MANE Select: NM_030627
dbSNP: rs1313241047
Type: single nucleotide variant
Location: chr5:173949529 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.58 · 3 PDB
Residue 493: the rrm 1 domain; a β-strand

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-arg493his (accessed [today's date]).

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