Is CPEB3 p.Val248Met (c.742G>A) pathogenic?

CPEB3 p.Val248Met (c.742G>A) is classified Uncertain significance in CPEB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.1084); Ultra-rare (popmax 0.019%, afr).

How common is CPEB3 p.Val248Met (c.742G>A) in the general population?

CPEB3 p.Val248Met (c.742G>A) is ultra-rare (popmax 0.019%, afr) (gnomAD).

What do computational predictors say about CPEB3 p.Val248Met (c.742G>A)?

AlphaMissense predicts likely benign (score 0.1084) — an in-silico prediction, not a clinical call.

CPEB3 p.Val248Met

c.742G>A · VCV4233288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1084	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.67	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 2.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 129 kb · p 0.0054 · regional, not allelic
Overall
CADD	26.5	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 0.019% African / African-American · 14/73,496 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00921%

Overall 0.00116% 18/1,556,286 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.019%	5,250
Remaining individualsnot grpmax-eligible	0.00332%	30,094
Finnishnot grpmax-eligible	0.00167%	59,928
European (non-Finnish)	8.69e-05%	1,150,140

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: CPEB3
Protein: p.Val248Met
Coding: c.742G>A
MANE Select: NM_014912
Type: single nucleotide variant
Location: chr10:92239609 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 58.59 · 6 PDB

Full CPEB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB3 p.Val280= Benign ★★ same type
CPEB3 p.Ala101Ser Uncertain significance ★ ⚠ same type
CPEB3 p.Ala118Thr Uncertain significance ★ ⚠ same type
CPEB3 p.Ala254Pro Uncertain significance ★ ⚠ same type
CPEB3 p.Ala388Thr Uncertain significance ★ ⚠ same type
CPEB3 p.Ala409Gly Uncertain significance ★ ⚠ same type
CPEB3 p.Ala61Val Uncertain significance ★ ⚠ same type
CPEB3 p.Ala64Thr 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/cpeb3-p-val248met (accessed [today's date]).

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