Is CPEB3 p.Arg337Trp (c.1009C>T) pathogenic?

CPEB3 p.Arg337Trp (c.1009C>T) is classified Uncertain significance in CPEB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9247); Very rare (popmax 0.00188%, amr).

How common is CPEB3 p.Arg337Trp (c.1009C>T) in the general population?

CPEB3 p.Arg337Trp (c.1009C>T) is very rare (popmax 0.00188%, amr) (gnomAD).

What do computational predictors say about CPEB3 p.Arg337Trp (c.1009C>T)?

AlphaMissense predicts likely pathogenic (score 0.9247) — an in-silico prediction, not a clinical call.

CPEB3 p.Arg337Trp

c.1009C>T · VCV4233299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00188%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9247	likely pathogenic
REVEL	0.491	indeterminate
SaProt	LLR -8.50	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.67 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 129 kb · p 0.0054 · regional, not allelic
Overall
CADD	34.0	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 0.00188% Admixed American · 1/53,144 alleles

Filtering AF 0.000891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000728%

Overall 0.00147% 21/1,423,852 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00329%	30,393
Admixed Americangrpmax	0.00188%	53,144
European (non-Finnish)	0.00146%	68,368
African / African-American	0.00136%	73,452

Remaining individuals 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: CPEB3
Protein: p.Arg337Trp
Coding: c.1009C>T
MANE Select: NM_014912
Type: single nucleotide variant
Location: chr10:92192633 (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-arg337trp (accessed [today's date]).

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