Is CPEB1 p.Ala109Val (c.326C>T) pathogenic?

CPEB1 p.Ala109Val (c.326C>T) is classified Uncertain significance in CPEB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Ultra-rare (popmax 0.0121%, sas).

How common is CPEB1 p.Ala109Val (c.326C>T) in the general population?

CPEB1 p.Ala109Val (c.326C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

CPEB1 p.Ala109Val

c.326C>T · rs374422926 · VCV3076620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.155	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,086 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.007% 113/1,614,172 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,281
European (non-Finnish)	0.0078%	12,826
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00533%	18,761
East Asian	0.00223%	44,876
Admixed American	0.00167%	60,028

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: CPEB1
Protein: p.Ala109Val
Coding: c.326C>T
MANE Select: NM_001365242
dbSNP: rs374422926
Type: single nucleotide variant
Location: chr15:82571478 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.05 · 5 PDB

Full CPEB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB1 p.Ala147Asp Uncertain significance ★ same type
CPEB1 p.Arg136Gly Uncertain significance ★ same type
CPEB1 p.Arg196Cys Uncertain significance ★ same type
CPEB1 p.Arg200Gln Uncertain significance ★ same type
CPEB1 p.Arg200Trp Uncertain significance ★ same type
CPEB1 p.Arg233His Uncertain significance ★ same type
CPEB1 p.Arg452Lys Uncertain significance ★ same type
CPEB1 p.Arg62Lys 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/cpeb1-p-ala109val (accessed [today's date]).

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