Is CPEB2 p.Pro317Ser (c.949C>T) pathogenic?

CPEB2 p.Pro317Ser (c.949C>T) is classified Uncertain significance in CPEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). Very rare (popmax 0.000446%, nfe).

How common is CPEB2 p.Pro317Ser (c.949C>T) in the general population?

CPEB2 p.Pro317Ser (c.949C>T) is very rare (popmax 0.000446%, nfe) (gnomAD).

CPEB2 p.Pro317Ser

c.949C>T · rs1173355186 · VCV2299086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000446%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.57, phastCons 1
Regional constraint	o/e 1.34	unconstrained · MANE · 50 kb · p 8.8e-28 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000446% European (non-Finnish) · 5/1,120,644 alleles

Filtering AF 0.000131% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.5e-05%

Overall 0.000376% 5/1,330,044 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: CPEB2
Protein: p.Pro317Ser
Coding: c.949C>T
MANE Select: NM_001177382
dbSNP: rs1173355186
Type: single nucleotide variant
Location: chr4:15003622 (GRCh38)
Gene constraint: LOEUF 1.328 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.86

Full CPEB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPEB2 p.Ala113Val Uncertain significance ★ same type
CPEB2 p.Ala27Val Uncertain significance ★ same type
CPEB2 p.Ala287Ser Uncertain significance ★ same type
CPEB2 p.Ala288Val Uncertain significance ★ same type
CPEB2 p.Ala494Ser Uncertain significance ★ same type
CPEB2 p.Ala517Thr Uncertain significance ★ same type
CPEB2 p.Ala540Val Uncertain significance ★ same type
CPEB2 p.Ala541Thr 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/cpeb2-p-pro317ser (accessed [today's date]).

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